Clinical Laboratories

Laboratory Director

High complexity CLIA laboratory director responsible for quality control supervision, laboratory safety, verification of appropriate personnel in the laboratory and technical experience, laboratory operating procedures review and proficiency testing review.

American Association for the Advancement of Science

On-Call Scientist

Human rights consultation related to chemical weapons and toxin exposures. Prior work with Amnesty International and other groups on issues related to Syria, Sudan, Iraq, and the Dakota Access Pipeline. https://oncallscientists.aaas.org/en

American Association for the Advancement of Science

On-Call Scientist Hotline

Human rights scientist selected to provide timely answers to one-off questions related to chemical weapons and toxin exposures. https://www.aaas.org/oncallscientistshotline

Toxicology Excellence for Risk Assessment

Member Board of Directors

Jennifer worked at Toxicology Excellence for Risk Assessment as a Member Board of Directors

CanMedLabs

Laboratory Director

Jennifer worked at CanMedLabs as a Laboratory Director

Mercer University, School of Pharmacy, Department of Pharmaceutical Sciences

Assistant Professor

Performed contracted analytical research of proteins, lipids, small molecules, and new drug products for both small and large companies including Shire Pharmaceuticals and L’Oréal with budgets ranging between $20,000 and $130,000.

Developed novel solid phase extraction – high performance liquid chromatography – mass spectrometry (SPE-HPLC-MS) and antibody affinity-HPLC/MS diagnostics for identifying and quantifying exposure to environmental and synthetic chemicals including paralytic shellfish poisons and pesticides.

Coordinator of the mass spectrometry facility and responsible for instrument maintenance, repair, use, and technical training of users.

Generated standardized operating procedures for analytical methods.

Developed microparticle delivery techniques for immunization against small molecule toxins.

Taught in and coordinated multiple pharmacy and graduate level courses including Gastrointestinal Disorders, Cardiovascular and Renal Disorders I and II, Immunology, and Analytical Methods and Instrumentation.

Noted Accomplishment: Chaired multiple committees within the college and university and participated in strategic planning and strategic direction for the college.

Commentary on Health and Environmental Risks from Hydraulic Fracturing

Hydraulic Fracturing Impacts and Technologies: A Multidisciplinary Perspective. CRC Press, Boca Raton

Petrochemical production has been happening in the United States since the 1900s.1 In the United States, total oil production had been declining for decades as shown in Figure 5.1. With the rise in oil prices, unconventional oil is now being recovered in everincreasing quantities. The International Energy Agency has dened unconventional oil as hydrocarbons that must be obtained using nontraditional technologies, which include hydraulic fracturing. Figure 5.2 presents the thousands of barrels produced per day from January 2000 through May 2011, highlighting the increase in tight oil production in the United States in recent years.

Commentary on Health and Environmental Risks from Hydraulic Fracturing

Hydraulic Fracturing Impacts and Technologies: A Multidisciplinary Perspective. CRC Press, Boca Raton

Petrochemical production has been happening in the United States since the 1900s.1 In the United States, total oil production had been declining for decades as shown in Figure 5.1. With the rise in oil prices, unconventional oil is now being recovered in everincreasing quantities. The International Energy Agency has dened unconventional oil as hydrocarbons that must be obtained using nontraditional technologies, which include hydraulic fracturing. Figure 5.2 presents the thousands of barrels produced per day from January 2000 through May 2011, highlighting the increase in tight oil production in the United States in recent years.

Cleaning and disinfecting environmental surfaces in health care: Toward an integrated framework for infection and occupational illness prevention

American Journal of Infection Control

BACKGROUND: The Cleaning and Disinfecting in Healthcare Working Group of the National Institute for Occupational Safety and Health, National Occupational Research Agenda, is a collaboration of infection prevention and occupational health researchers and practitioners with the objective of providing a more integrated approach to effective environmental surface cleaning and disinfection (C&D) while protecting the respiratory health of health care personnel. METHODS: The Working Group, comprised of >40 members from 4 countries, reviewed current knowledge and identified knowledge gaps and future needs for research and practice. RESULTS: An integrated framework was developed to guide more comprehensive efforts to minimize harmful C&D exposures without reducing the effectiveness of infection prevention. Gaps in basic knowledge and practice that are barriers to an integrated approach were grouped in 2 broad areas related to the need for improved understanding of the (1) effectiveness of environmental surface C&D to reduce the incidence of infectious diseases and colonization in health care workers and patients and (2) adverse health impacts of C&D on health care workers and patients. Specific needs identified within each area relate to basic knowledge, improved selection and use of products and practices, effective hazard communication and training, and safer alternatives. CONCLUSION: A more integrated approach can support multidisciplinary teams with the capacity to maximize effective and safe C&D in health care.

Commentary on Health and Environmental Risks from Hydraulic Fracturing

Hydraulic Fracturing Impacts and Technologies: A Multidisciplinary Perspective. CRC Press, Boca Raton

Petrochemical production has been happening in the United States since the 1900s.1 In the United States, total oil production had been declining for decades as shown in Figure 5.1. With the rise in oil prices, unconventional oil is now being recovered in everincreasing quantities. The International Energy Agency has dened unconventional oil as hydrocarbons that must be obtained using nontraditional technologies, which include hydraulic fracturing. Figure 5.2 presents the thousands of barrels produced per day from January 2000 through May 2011, highlighting the increase in tight oil production in the United States in recent years.

Cleaning and disinfecting environmental surfaces in health care: Toward an integrated framework for infection and occupational illness prevention

American Journal of Infection Control

BACKGROUND: The Cleaning and Disinfecting in Healthcare Working Group of the National Institute for Occupational Safety and Health, National Occupational Research Agenda, is a collaboration of infection prevention and occupational health researchers and practitioners with the objective of providing a more integrated approach to effective environmental surface cleaning and disinfection (C&D) while protecting the respiratory health of health care personnel. METHODS: The Working Group, comprised of >40 members from 4 countries, reviewed current knowledge and identified knowledge gaps and future needs for research and practice. RESULTS: An integrated framework was developed to guide more comprehensive efforts to minimize harmful C&D exposures without reducing the effectiveness of infection prevention. Gaps in basic knowledge and practice that are barriers to an integrated approach were grouped in 2 broad areas related to the need for improved understanding of the (1) effectiveness of environmental surface C&D to reduce the incidence of infectious diseases and colonization in health care workers and patients and (2) adverse health impacts of C&D on health care workers and patients. Specific needs identified within each area relate to basic knowledge, improved selection and use of products and practices, effective hazard communication and training, and safer alternatives. CONCLUSION: A more integrated approach can support multidisciplinary teams with the capacity to maximize effective and safe C&D in health care.

Chemical Weapons Use in Jebel Marra – Analysis of Symptoms and Potential Agents Used

Public Interest Report, Federation of American Scientists

Commentary on Health and Environmental Risks from Hydraulic Fracturing

Hydraulic Fracturing Impacts and Technologies: A Multidisciplinary Perspective. CRC Press, Boca Raton

Petrochemical production has been happening in the United States since the 1900s.1 In the United States, total oil production had been declining for decades as shown in Figure 5.1. With the rise in oil prices, unconventional oil is now being recovered in everincreasing quantities. The International Energy Agency has dened unconventional oil as hydrocarbons that must be obtained using nontraditional technologies, which include hydraulic fracturing. Figure 5.2 presents the thousands of barrels produced per day from January 2000 through May 2011, highlighting the increase in tight oil production in the United States in recent years.

Cleaning and disinfecting environmental surfaces in health care: Toward an integrated framework for infection and occupational illness prevention

American Journal of Infection Control

BACKGROUND: The Cleaning and Disinfecting in Healthcare Working Group of the National Institute for Occupational Safety and Health, National Occupational Research Agenda, is a collaboration of infection prevention and occupational health researchers and practitioners with the objective of providing a more integrated approach to effective environmental surface cleaning and disinfection (C&D) while protecting the respiratory health of health care personnel. METHODS: The Working Group, comprised of >40 members from 4 countries, reviewed current knowledge and identified knowledge gaps and future needs for research and practice. RESULTS: An integrated framework was developed to guide more comprehensive efforts to minimize harmful C&D exposures without reducing the effectiveness of infection prevention. Gaps in basic knowledge and practice that are barriers to an integrated approach were grouped in 2 broad areas related to the need for improved understanding of the (1) effectiveness of environmental surface C&D to reduce the incidence of infectious diseases and colonization in health care workers and patients and (2) adverse health impacts of C&D on health care workers and patients. Specific needs identified within each area relate to basic knowledge, improved selection and use of products and practices, effective hazard communication and training, and safer alternatives. CONCLUSION: A more integrated approach can support multidisciplinary teams with the capacity to maximize effective and safe C&D in health care.

Chemical Weapons Use in Jebel Marra – Analysis of Symptoms and Potential Agents Used

Public Interest Report, Federation of American Scientists

Case diagnosis and characterization of suspected paralytic shellfish poisoning in Alaska

Harmful Algae

Clinical cases of paralytic shellfish poisoning (PSP) are common in Alaska, and result from human consumption of shellfish contaminated with saxitoxin (STX) and its analogues. Diagnosis of PSP is presumptive and based on recent ingestion of shellfish and presence of manifestations consistent with symptoms of PSP; diagnosis is confirmed by detection of paralytic shellfish toxins in a clinical specimen or food sample. A clinical diagnostic analytical method using high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) was used to evaluate the diagnosis of saxitoxin-induced PSP (STX-PSP) in 11 Alaskan patients using urine specimens collected between June 2010 and November 2011. Concentrations of urinary STX were corrected for creatinine concentrations to account for dilution or concentration of urine from water intake or restriction, respectively. Of the 11 patients with suspected PSP, four patients were confirmed to have STX-PSP by urine testing (24-364ng STX/g creatinine). Five patients had clinical manifestations of PSP though no STX was detected in their urine. Two patients were ruled out for STX-PSP based on non-detected urinary STX and the absence of clinical findings. Results revealed that dysphagia and dysarthria may be stronger indicators of PSP than paresthesia and nausea, which are commonly used to clinically diagnose patients with PSP. PSP can also occur from exposure to a number of STX congeners, such as gonyautoxins, however their presence in urine was not assessed in this investigation. In addition, meal remnants obtained from six presumptive PSP cases were analyzed using the Association of Official Analytical Chemists' mouse bioassay. All six samples tested positive for PSP toxins. In the future, the clinical diagnostic method can be used in conjunction with the mouse bioassay or HPLC-MS/MS to assess the extent of STX-PSP in Alaska where it has been suggested that PSP is underreported.

Commentary on Health and Environmental Risks from Hydraulic Fracturing

Hydraulic Fracturing Impacts and Technologies: A Multidisciplinary Perspective. CRC Press, Boca Raton

Petrochemical production has been happening in the United States since the 1900s.1 In the United States, total oil production had been declining for decades as shown in Figure 5.1. With the rise in oil prices, unconventional oil is now being recovered in everincreasing quantities. The International Energy Agency has dened unconventional oil as hydrocarbons that must be obtained using nontraditional technologies, which include hydraulic fracturing. Figure 5.2 presents the thousands of barrels produced per day from January 2000 through May 2011, highlighting the increase in tight oil production in the United States in recent years.

Cleaning and disinfecting environmental surfaces in health care: Toward an integrated framework for infection and occupational illness prevention

American Journal of Infection Control

BACKGROUND: The Cleaning and Disinfecting in Healthcare Working Group of the National Institute for Occupational Safety and Health, National Occupational Research Agenda, is a collaboration of infection prevention and occupational health researchers and practitioners with the objective of providing a more integrated approach to effective environmental surface cleaning and disinfection (C&D) while protecting the respiratory health of health care personnel. METHODS: The Working Group, comprised of >40 members from 4 countries, reviewed current knowledge and identified knowledge gaps and future needs for research and practice. RESULTS: An integrated framework was developed to guide more comprehensive efforts to minimize harmful C&D exposures without reducing the effectiveness of infection prevention. Gaps in basic knowledge and practice that are barriers to an integrated approach were grouped in 2 broad areas related to the need for improved understanding of the (1) effectiveness of environmental surface C&D to reduce the incidence of infectious diseases and colonization in health care workers and patients and (2) adverse health impacts of C&D on health care workers and patients. Specific needs identified within each area relate to basic knowledge, improved selection and use of products and practices, effective hazard communication and training, and safer alternatives. CONCLUSION: A more integrated approach can support multidisciplinary teams with the capacity to maximize effective and safe C&D in health care.

Chemical Weapons Use in Jebel Marra – Analysis of Symptoms and Potential Agents Used

Public Interest Report, Federation of American Scientists

Case diagnosis and characterization of suspected paralytic shellfish poisoning in Alaska

Harmful Algae

Clinical cases of paralytic shellfish poisoning (PSP) are common in Alaska, and result from human consumption of shellfish contaminated with saxitoxin (STX) and its analogues. Diagnosis of PSP is presumptive and based on recent ingestion of shellfish and presence of manifestations consistent with symptoms of PSP; diagnosis is confirmed by detection of paralytic shellfish toxins in a clinical specimen or food sample. A clinical diagnostic analytical method using high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) was used to evaluate the diagnosis of saxitoxin-induced PSP (STX-PSP) in 11 Alaskan patients using urine specimens collected between June 2010 and November 2011. Concentrations of urinary STX were corrected for creatinine concentrations to account for dilution or concentration of urine from water intake or restriction, respectively. Of the 11 patients with suspected PSP, four patients were confirmed to have STX-PSP by urine testing (24-364ng STX/g creatinine). Five patients had clinical manifestations of PSP though no STX was detected in their urine. Two patients were ruled out for STX-PSP based on non-detected urinary STX and the absence of clinical findings. Results revealed that dysphagia and dysarthria may be stronger indicators of PSP than paresthesia and nausea, which are commonly used to clinically diagnose patients with PSP. PSP can also occur from exposure to a number of STX congeners, such as gonyautoxins, however their presence in urine was not assessed in this investigation. In addition, meal remnants obtained from six presumptive PSP cases were analyzed using the Association of Official Analytical Chemists' mouse bioassay. All six samples tested positive for PSP toxins. In the future, the clinical diagnostic method can be used in conjunction with the mouse bioassay or HPLC-MS/MS to assess the extent of STX-PSP in Alaska where it has been suggested that PSP is underreported.

Quantitative analysis and stability of the rodenticide TETS (tetramine) in finished tap water

Analytical Methods

The determination of the rodenticide tetramethylenedisulfotetramine (TETS) in drinking water is reportable through the use of automated sample preparation via solid phase extraction and detection using isotope dilution gas chromatography-mass spectrometry. The method was characterized over twenty-two analytical batches with quality control samples. Accuracies for low and high concentration quality control pools were 100 and 101%, respectively. The minimum reporting level (MRL) for TETS in this method is 0.50 μg L−1. Five drinking waters representing a range of water quality parameters and disinfection practices were fortified with TETS at ten times the MRL and analyzed over a 28 day period to determine the stability of TETS in these waters. The amount of TETS measured in these samples averaged 100 ± 6% of the amount fortified suggesting that tap water samples may be held for up to 28 days prior to analysis.

Commentary on Health and Environmental Risks from Hydraulic Fracturing

Hydraulic Fracturing Impacts and Technologies: A Multidisciplinary Perspective. CRC Press, Boca Raton

Petrochemical production has been happening in the United States since the 1900s.1 In the United States, total oil production had been declining for decades as shown in Figure 5.1. With the rise in oil prices, unconventional oil is now being recovered in everincreasing quantities. The International Energy Agency has dened unconventional oil as hydrocarbons that must be obtained using nontraditional technologies, which include hydraulic fracturing. Figure 5.2 presents the thousands of barrels produced per day from January 2000 through May 2011, highlighting the increase in tight oil production in the United States in recent years.

Cleaning and disinfecting environmental surfaces in health care: Toward an integrated framework for infection and occupational illness prevention

American Journal of Infection Control

BACKGROUND: The Cleaning and Disinfecting in Healthcare Working Group of the National Institute for Occupational Safety and Health, National Occupational Research Agenda, is a collaboration of infection prevention and occupational health researchers and practitioners with the objective of providing a more integrated approach to effective environmental surface cleaning and disinfection (C&D) while protecting the respiratory health of health care personnel. METHODS: The Working Group, comprised of >40 members from 4 countries, reviewed current knowledge and identified knowledge gaps and future needs for research and practice. RESULTS: An integrated framework was developed to guide more comprehensive efforts to minimize harmful C&D exposures without reducing the effectiveness of infection prevention. Gaps in basic knowledge and practice that are barriers to an integrated approach were grouped in 2 broad areas related to the need for improved understanding of the (1) effectiveness of environmental surface C&D to reduce the incidence of infectious diseases and colonization in health care workers and patients and (2) adverse health impacts of C&D on health care workers and patients. Specific needs identified within each area relate to basic knowledge, improved selection and use of products and practices, effective hazard communication and training, and safer alternatives. CONCLUSION: A more integrated approach can support multidisciplinary teams with the capacity to maximize effective and safe C&D in health care.

Chemical Weapons Use in Jebel Marra – Analysis of Symptoms and Potential Agents Used

Public Interest Report, Federation of American Scientists

Case diagnosis and characterization of suspected paralytic shellfish poisoning in Alaska

Harmful Algae

Clinical cases of paralytic shellfish poisoning (PSP) are common in Alaska, and result from human consumption of shellfish contaminated with saxitoxin (STX) and its analogues. Diagnosis of PSP is presumptive and based on recent ingestion of shellfish and presence of manifestations consistent with symptoms of PSP; diagnosis is confirmed by detection of paralytic shellfish toxins in a clinical specimen or food sample. A clinical diagnostic analytical method using high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) was used to evaluate the diagnosis of saxitoxin-induced PSP (STX-PSP) in 11 Alaskan patients using urine specimens collected between June 2010 and November 2011. Concentrations of urinary STX were corrected for creatinine concentrations to account for dilution or concentration of urine from water intake or restriction, respectively. Of the 11 patients with suspected PSP, four patients were confirmed to have STX-PSP by urine testing (24-364ng STX/g creatinine). Five patients had clinical manifestations of PSP though no STX was detected in their urine. Two patients were ruled out for STX-PSP based on non-detected urinary STX and the absence of clinical findings. Results revealed that dysphagia and dysarthria may be stronger indicators of PSP than paresthesia and nausea, which are commonly used to clinically diagnose patients with PSP. PSP can also occur from exposure to a number of STX congeners, such as gonyautoxins, however their presence in urine was not assessed in this investigation. In addition, meal remnants obtained from six presumptive PSP cases were analyzed using the Association of Official Analytical Chemists' mouse bioassay. All six samples tested positive for PSP toxins. In the future, the clinical diagnostic method can be used in conjunction with the mouse bioassay or HPLC-MS/MS to assess the extent of STX-PSP in Alaska where it has been suggested that PSP is underreported.

Quantitative analysis and stability of the rodenticide TETS (tetramine) in finished tap water

Analytical Methods

The determination of the rodenticide tetramethylenedisulfotetramine (TETS) in drinking water is reportable through the use of automated sample preparation via solid phase extraction and detection using isotope dilution gas chromatography-mass spectrometry. The method was characterized over twenty-two analytical batches with quality control samples. Accuracies for low and high concentration quality control pools were 100 and 101%, respectively. The minimum reporting level (MRL) for TETS in this method is 0.50 μg L−1. Five drinking waters representing a range of water quality parameters and disinfection practices were fortified with TETS at ten times the MRL and analyzed over a 28 day period to determine the stability of TETS in these waters. The amount of TETS measured in these samples averaged 100 ± 6% of the amount fortified suggesting that tap water samples may be held for up to 28 days prior to analysis.

Method Development for Extraction of Butyrylcholinesterase Using Protein-G Agarose Spin Columns

Journal of Applied Bioanalysis

Butyrylcholinesterase (BuChE) is a biomarker of organophosphate (OP) poisoning and can be used as a diagnostic marker to measure exposure to OP compounds. The purpose of this study was to develop a method to extract BuChE from human plasma. BuChE was extracted from plasma using the NAb protein-G Agarose Spin Kit. Factors affecting extraction like incubation time, plasma volume and cross-linking of antibodies to agarose beads were evaluated. All samples were analyzed for BuChE activity using the Ellman’s assay. The incubation times of plasma and anti-BuChE antibodies marginally affected the extraction efficiency of BuChE whereas a decrease in plasma volume increased the extraction efficiency. Cross-linking of anti-BuChE antibodies on agarose increased the extraction efficiency. The NAb protein-G Spin Kit can be used successfully to extract BuChE from human plasma. This extraction technique may be coupled to downstream analytical analyses for diagnosing exposure to OP compounds.

Commentary on Health and Environmental Risks from Hydraulic Fracturing

Hydraulic Fracturing Impacts and Technologies: A Multidisciplinary Perspective. CRC Press, Boca Raton

Petrochemical production has been happening in the United States since the 1900s.1 In the United States, total oil production had been declining for decades as shown in Figure 5.1. With the rise in oil prices, unconventional oil is now being recovered in everincreasing quantities. The International Energy Agency has dened unconventional oil as hydrocarbons that must be obtained using nontraditional technologies, which include hydraulic fracturing. Figure 5.2 presents the thousands of barrels produced per day from January 2000 through May 2011, highlighting the increase in tight oil production in the United States in recent years.

Cleaning and disinfecting environmental surfaces in health care: Toward an integrated framework for infection and occupational illness prevention

American Journal of Infection Control

BACKGROUND: The Cleaning and Disinfecting in Healthcare Working Group of the National Institute for Occupational Safety and Health, National Occupational Research Agenda, is a collaboration of infection prevention and occupational health researchers and practitioners with the objective of providing a more integrated approach to effective environmental surface cleaning and disinfection (C&D) while protecting the respiratory health of health care personnel. METHODS: The Working Group, comprised of >40 members from 4 countries, reviewed current knowledge and identified knowledge gaps and future needs for research and practice. RESULTS: An integrated framework was developed to guide more comprehensive efforts to minimize harmful C&D exposures without reducing the effectiveness of infection prevention. Gaps in basic knowledge and practice that are barriers to an integrated approach were grouped in 2 broad areas related to the need for improved understanding of the (1) effectiveness of environmental surface C&D to reduce the incidence of infectious diseases and colonization in health care workers and patients and (2) adverse health impacts of C&D on health care workers and patients. Specific needs identified within each area relate to basic knowledge, improved selection and use of products and practices, effective hazard communication and training, and safer alternatives. CONCLUSION: A more integrated approach can support multidisciplinary teams with the capacity to maximize effective and safe C&D in health care.

Chemical Weapons Use in Jebel Marra – Analysis of Symptoms and Potential Agents Used

Public Interest Report, Federation of American Scientists

Case diagnosis and characterization of suspected paralytic shellfish poisoning in Alaska

Harmful Algae

Clinical cases of paralytic shellfish poisoning (PSP) are common in Alaska, and result from human consumption of shellfish contaminated with saxitoxin (STX) and its analogues. Diagnosis of PSP is presumptive and based on recent ingestion of shellfish and presence of manifestations consistent with symptoms of PSP; diagnosis is confirmed by detection of paralytic shellfish toxins in a clinical specimen or food sample. A clinical diagnostic analytical method using high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) was used to evaluate the diagnosis of saxitoxin-induced PSP (STX-PSP) in 11 Alaskan patients using urine specimens collected between June 2010 and November 2011. Concentrations of urinary STX were corrected for creatinine concentrations to account for dilution or concentration of urine from water intake or restriction, respectively. Of the 11 patients with suspected PSP, four patients were confirmed to have STX-PSP by urine testing (24-364ng STX/g creatinine). Five patients had clinical manifestations of PSP though no STX was detected in their urine. Two patients were ruled out for STX-PSP based on non-detected urinary STX and the absence of clinical findings. Results revealed that dysphagia and dysarthria may be stronger indicators of PSP than paresthesia and nausea, which are commonly used to clinically diagnose patients with PSP. PSP can also occur from exposure to a number of STX congeners, such as gonyautoxins, however their presence in urine was not assessed in this investigation. In addition, meal remnants obtained from six presumptive PSP cases were analyzed using the Association of Official Analytical Chemists' mouse bioassay. All six samples tested positive for PSP toxins. In the future, the clinical diagnostic method can be used in conjunction with the mouse bioassay or HPLC-MS/MS to assess the extent of STX-PSP in Alaska where it has been suggested that PSP is underreported.

Quantitative analysis and stability of the rodenticide TETS (tetramine) in finished tap water

Analytical Methods

The determination of the rodenticide tetramethylenedisulfotetramine (TETS) in drinking water is reportable through the use of automated sample preparation via solid phase extraction and detection using isotope dilution gas chromatography-mass spectrometry. The method was characterized over twenty-two analytical batches with quality control samples. Accuracies for low and high concentration quality control pools were 100 and 101%, respectively. The minimum reporting level (MRL) for TETS in this method is 0.50 μg L−1. Five drinking waters representing a range of water quality parameters and disinfection practices were fortified with TETS at ten times the MRL and analyzed over a 28 day period to determine the stability of TETS in these waters. The amount of TETS measured in these samples averaged 100 ± 6% of the amount fortified suggesting that tap water samples may be held for up to 28 days prior to analysis.

Method Development for Extraction of Butyrylcholinesterase Using Protein-G Agarose Spin Columns

Journal of Applied Bioanalysis

Butyrylcholinesterase (BuChE) is a biomarker of organophosphate (OP) poisoning and can be used as a diagnostic marker to measure exposure to OP compounds. The purpose of this study was to develop a method to extract BuChE from human plasma. BuChE was extracted from plasma using the NAb protein-G Agarose Spin Kit. Factors affecting extraction like incubation time, plasma volume and cross-linking of antibodies to agarose beads were evaluated. All samples were analyzed for BuChE activity using the Ellman’s assay. The incubation times of plasma and anti-BuChE antibodies marginally affected the extraction efficiency of BuChE whereas a decrease in plasma volume increased the extraction efficiency. Cross-linking of anti-BuChE antibodies on agarose increased the extraction efficiency. The NAb protein-G Spin Kit can be used successfully to extract BuChE from human plasma. This extraction technique may be coupled to downstream analytical analyses for diagnosing exposure to OP compounds.

Dihydroergotamine mesylate-loaded dissolving microneedle patch made of polyvinylpyrrolidone for management of acute migraine therapy

Journal of Controlled Release

Abstract Migraine is a widespread neurological disease with negative effects on quality of life and productivity. Moderate to severe acute migraine attacks can be treated with dihydroergotamine mesylate (DHE), an ergot derivative that is especially effective in non-responders to triptan derivatives. To overcome limitations of current DHE formulations in subcutaneous injection and nasal spray such as pain, adverse side effects and poor bioavailability, a new approach is needed for DHE delivery enabling painless self-administration, quick onset of action, and high bioavailability. In this study, we developed a dissolving microneedle patch (MNP) made of polyvinylpyrrolidone, due to its high aqueous solubility and solubility enhancement properties, using a MNP design previously shown to be painless and simple to administer. DHE-loaded MNPs were shown to have a content uniformity of 108±9% with sufficient mechanical strength for insertion to pig skin ex vivo and dissolution within 2min. In vivo pharmacokinetic studies were carried out on hairless rats, and DHE plasma levels were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The area under curve (AUC) value after DHE delivery by MNP (1259±917ng/mL min) was not significantly different (p>0.05) as compared to subcutaneous injection, with a relative bioavailability of 97%. Also, appreciable plasma levels of DHE were seen within 5min for both delivery methods and tmax value of MNPs (38±23min) showed no significant difference (p>0.05) compared to subcutaneous injection (24±13min). These results suggest that DHE-loaded MNPs have promise as an alternative DHE delivery method that can be painlessly self-administered with rapid onset and high bioavailability.

Commentary on Health and Environmental Risks from Hydraulic Fracturing

Hydraulic Fracturing Impacts and Technologies: A Multidisciplinary Perspective. CRC Press, Boca Raton

Petrochemical production has been happening in the United States since the 1900s.1 In the United States, total oil production had been declining for decades as shown in Figure 5.1. With the rise in oil prices, unconventional oil is now being recovered in everincreasing quantities. The International Energy Agency has dened unconventional oil as hydrocarbons that must be obtained using nontraditional technologies, which include hydraulic fracturing. Figure 5.2 presents the thousands of barrels produced per day from January 2000 through May 2011, highlighting the increase in tight oil production in the United States in recent years.

Cleaning and disinfecting environmental surfaces in health care: Toward an integrated framework for infection and occupational illness prevention

American Journal of Infection Control

BACKGROUND: The Cleaning and Disinfecting in Healthcare Working Group of the National Institute for Occupational Safety and Health, National Occupational Research Agenda, is a collaboration of infection prevention and occupational health researchers and practitioners with the objective of providing a more integrated approach to effective environmental surface cleaning and disinfection (C&D) while protecting the respiratory health of health care personnel. METHODS: The Working Group, comprised of >40 members from 4 countries, reviewed current knowledge and identified knowledge gaps and future needs for research and practice. RESULTS: An integrated framework was developed to guide more comprehensive efforts to minimize harmful C&D exposures without reducing the effectiveness of infection prevention. Gaps in basic knowledge and practice that are barriers to an integrated approach were grouped in 2 broad areas related to the need for improved understanding of the (1) effectiveness of environmental surface C&D to reduce the incidence of infectious diseases and colonization in health care workers and patients and (2) adverse health impacts of C&D on health care workers and patients. Specific needs identified within each area relate to basic knowledge, improved selection and use of products and practices, effective hazard communication and training, and safer alternatives. CONCLUSION: A more integrated approach can support multidisciplinary teams with the capacity to maximize effective and safe C&D in health care.

Chemical Weapons Use in Jebel Marra – Analysis of Symptoms and Potential Agents Used

Public Interest Report, Federation of American Scientists

Case diagnosis and characterization of suspected paralytic shellfish poisoning in Alaska

Harmful Algae

Clinical cases of paralytic shellfish poisoning (PSP) are common in Alaska, and result from human consumption of shellfish contaminated with saxitoxin (STX) and its analogues. Diagnosis of PSP is presumptive and based on recent ingestion of shellfish and presence of manifestations consistent with symptoms of PSP; diagnosis is confirmed by detection of paralytic shellfish toxins in a clinical specimen or food sample. A clinical diagnostic analytical method using high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) was used to evaluate the diagnosis of saxitoxin-induced PSP (STX-PSP) in 11 Alaskan patients using urine specimens collected between June 2010 and November 2011. Concentrations of urinary STX were corrected for creatinine concentrations to account for dilution or concentration of urine from water intake or restriction, respectively. Of the 11 patients with suspected PSP, four patients were confirmed to have STX-PSP by urine testing (24-364ng STX/g creatinine). Five patients had clinical manifestations of PSP though no STX was detected in their urine. Two patients were ruled out for STX-PSP based on non-detected urinary STX and the absence of clinical findings. Results revealed that dysphagia and dysarthria may be stronger indicators of PSP than paresthesia and nausea, which are commonly used to clinically diagnose patients with PSP. PSP can also occur from exposure to a number of STX congeners, such as gonyautoxins, however their presence in urine was not assessed in this investigation. In addition, meal remnants obtained from six presumptive PSP cases were analyzed using the Association of Official Analytical Chemists' mouse bioassay. All six samples tested positive for PSP toxins. In the future, the clinical diagnostic method can be used in conjunction with the mouse bioassay or HPLC-MS/MS to assess the extent of STX-PSP in Alaska where it has been suggested that PSP is underreported.

Quantitative analysis and stability of the rodenticide TETS (tetramine) in finished tap water

Analytical Methods

The determination of the rodenticide tetramethylenedisulfotetramine (TETS) in drinking water is reportable through the use of automated sample preparation via solid phase extraction and detection using isotope dilution gas chromatography-mass spectrometry. The method was characterized over twenty-two analytical batches with quality control samples. Accuracies for low and high concentration quality control pools were 100 and 101%, respectively. The minimum reporting level (MRL) for TETS in this method is 0.50 μg L−1. Five drinking waters representing a range of water quality parameters and disinfection practices were fortified with TETS at ten times the MRL and analyzed over a 28 day period to determine the stability of TETS in these waters. The amount of TETS measured in these samples averaged 100 ± 6% of the amount fortified suggesting that tap water samples may be held for up to 28 days prior to analysis.

Method Development for Extraction of Butyrylcholinesterase Using Protein-G Agarose Spin Columns

Journal of Applied Bioanalysis

Butyrylcholinesterase (BuChE) is a biomarker of organophosphate (OP) poisoning and can be used as a diagnostic marker to measure exposure to OP compounds. The purpose of this study was to develop a method to extract BuChE from human plasma. BuChE was extracted from plasma using the NAb protein-G Agarose Spin Kit. Factors affecting extraction like incubation time, plasma volume and cross-linking of antibodies to agarose beads were evaluated. All samples were analyzed for BuChE activity using the Ellman’s assay. The incubation times of plasma and anti-BuChE antibodies marginally affected the extraction efficiency of BuChE whereas a decrease in plasma volume increased the extraction efficiency. Cross-linking of anti-BuChE antibodies on agarose increased the extraction efficiency. The NAb protein-G Spin Kit can be used successfully to extract BuChE from human plasma. This extraction technique may be coupled to downstream analytical analyses for diagnosing exposure to OP compounds.

Dihydroergotamine mesylate-loaded dissolving microneedle patch made of polyvinylpyrrolidone for management of acute migraine therapy

Journal of Controlled Release

Abstract Migraine is a widespread neurological disease with negative effects on quality of life and productivity. Moderate to severe acute migraine attacks can be treated with dihydroergotamine mesylate (DHE), an ergot derivative that is especially effective in non-responders to triptan derivatives. To overcome limitations of current DHE formulations in subcutaneous injection and nasal spray such as pain, adverse side effects and poor bioavailability, a new approach is needed for DHE delivery enabling painless self-administration, quick onset of action, and high bioavailability. In this study, we developed a dissolving microneedle patch (MNP) made of polyvinylpyrrolidone, due to its high aqueous solubility and solubility enhancement properties, using a MNP design previously shown to be painless and simple to administer. DHE-loaded MNPs were shown to have a content uniformity of 108±9% with sufficient mechanical strength for insertion to pig skin ex vivo and dissolution within 2min. In vivo pharmacokinetic studies were carried out on hairless rats, and DHE plasma levels were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The area under curve (AUC) value after DHE delivery by MNP (1259±917ng/mL min) was not significantly different (p>0.05) as compared to subcutaneous injection, with a relative bioavailability of 97%. Also, appreciable plasma levels of DHE were seen within 5min for both delivery methods and tmax value of MNPs (38±23min) showed no significant difference (p>0.05) compared to subcutaneous injection (24±13min). These results suggest that DHE-loaded MNPs have promise as an alternative DHE delivery method that can be painlessly self-administered with rapid onset and high bioavailability.

Monitoring drug pharmacokinetics and immunologic biomarkers in dermal interstitial fluid using a microneedle patch

Biomedical Microdevices

Minimally invasive point-of-care diagnostic devices are of great interest for rapid detection of biomarkers in diverse settings. Although blood is the most common source of biomarkers, interstitial fluid (ISF) is an alternate body fluid that does not clot or contain red blood cells that often complicate analysis. However, ISF is difficult to collect. In this study, we assessed the utility of a microneedle patch to sample microliter volumes of ISF in a simple and minimally invasive manner. We demonstrated the use of ISF collected in this way for therapeutic drug monitoring by showing similar vancomycin pharmacokinetic profiles in ISF and serum from rats. We also measured polio-specific neutralizing antibodies and anti-polio IgG in ISF similar to serum in rats immunized with polio vaccine. These studies demonstrate the potential utility of ISF collected by microneedle patch in therapeutic drug monitoring and immunodiagnostic applications.

Commentary on Health and Environmental Risks from Hydraulic Fracturing

Hydraulic Fracturing Impacts and Technologies: A Multidisciplinary Perspective. CRC Press, Boca Raton

Petrochemical production has been happening in the United States since the 1900s.1 In the United States, total oil production had been declining for decades as shown in Figure 5.1. With the rise in oil prices, unconventional oil is now being recovered in everincreasing quantities. The International Energy Agency has dened unconventional oil as hydrocarbons that must be obtained using nontraditional technologies, which include hydraulic fracturing. Figure 5.2 presents the thousands of barrels produced per day from January 2000 through May 2011, highlighting the increase in tight oil production in the United States in recent years.

Cleaning and disinfecting environmental surfaces in health care: Toward an integrated framework for infection and occupational illness prevention

American Journal of Infection Control

BACKGROUND: The Cleaning and Disinfecting in Healthcare Working Group of the National Institute for Occupational Safety and Health, National Occupational Research Agenda, is a collaboration of infection prevention and occupational health researchers and practitioners with the objective of providing a more integrated approach to effective environmental surface cleaning and disinfection (C&D) while protecting the respiratory health of health care personnel. METHODS: The Working Group, comprised of >40 members from 4 countries, reviewed current knowledge and identified knowledge gaps and future needs for research and practice. RESULTS: An integrated framework was developed to guide more comprehensive efforts to minimize harmful C&D exposures without reducing the effectiveness of infection prevention. Gaps in basic knowledge and practice that are barriers to an integrated approach were grouped in 2 broad areas related to the need for improved understanding of the (1) effectiveness of environmental surface C&D to reduce the incidence of infectious diseases and colonization in health care workers and patients and (2) adverse health impacts of C&D on health care workers and patients. Specific needs identified within each area relate to basic knowledge, improved selection and use of products and practices, effective hazard communication and training, and safer alternatives. CONCLUSION: A more integrated approach can support multidisciplinary teams with the capacity to maximize effective and safe C&D in health care.

Chemical Weapons Use in Jebel Marra – Analysis of Symptoms and Potential Agents Used

Public Interest Report, Federation of American Scientists

Case diagnosis and characterization of suspected paralytic shellfish poisoning in Alaska

Harmful Algae

Clinical cases of paralytic shellfish poisoning (PSP) are common in Alaska, and result from human consumption of shellfish contaminated with saxitoxin (STX) and its analogues. Diagnosis of PSP is presumptive and based on recent ingestion of shellfish and presence of manifestations consistent with symptoms of PSP; diagnosis is confirmed by detection of paralytic shellfish toxins in a clinical specimen or food sample. A clinical diagnostic analytical method using high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) was used to evaluate the diagnosis of saxitoxin-induced PSP (STX-PSP) in 11 Alaskan patients using urine specimens collected between June 2010 and November 2011. Concentrations of urinary STX were corrected for creatinine concentrations to account for dilution or concentration of urine from water intake or restriction, respectively. Of the 11 patients with suspected PSP, four patients were confirmed to have STX-PSP by urine testing (24-364ng STX/g creatinine). Five patients had clinical manifestations of PSP though no STX was detected in their urine. Two patients were ruled out for STX-PSP based on non-detected urinary STX and the absence of clinical findings. Results revealed that dysphagia and dysarthria may be stronger indicators of PSP than paresthesia and nausea, which are commonly used to clinically diagnose patients with PSP. PSP can also occur from exposure to a number of STX congeners, such as gonyautoxins, however their presence in urine was not assessed in this investigation. In addition, meal remnants obtained from six presumptive PSP cases were analyzed using the Association of Official Analytical Chemists' mouse bioassay. All six samples tested positive for PSP toxins. In the future, the clinical diagnostic method can be used in conjunction with the mouse bioassay or HPLC-MS/MS to assess the extent of STX-PSP in Alaska where it has been suggested that PSP is underreported.

Quantitative analysis and stability of the rodenticide TETS (tetramine) in finished tap water

Analytical Methods

The determination of the rodenticide tetramethylenedisulfotetramine (TETS) in drinking water is reportable through the use of automated sample preparation via solid phase extraction and detection using isotope dilution gas chromatography-mass spectrometry. The method was characterized over twenty-two analytical batches with quality control samples. Accuracies for low and high concentration quality control pools were 100 and 101%, respectively. The minimum reporting level (MRL) for TETS in this method is 0.50 μg L−1. Five drinking waters representing a range of water quality parameters and disinfection practices were fortified with TETS at ten times the MRL and analyzed over a 28 day period to determine the stability of TETS in these waters. The amount of TETS measured in these samples averaged 100 ± 6% of the amount fortified suggesting that tap water samples may be held for up to 28 days prior to analysis.

Method Development for Extraction of Butyrylcholinesterase Using Protein-G Agarose Spin Columns

Journal of Applied Bioanalysis

Butyrylcholinesterase (BuChE) is a biomarker of organophosphate (OP) poisoning and can be used as a diagnostic marker to measure exposure to OP compounds. The purpose of this study was to develop a method to extract BuChE from human plasma. BuChE was extracted from plasma using the NAb protein-G Agarose Spin Kit. Factors affecting extraction like incubation time, plasma volume and cross-linking of antibodies to agarose beads were evaluated. All samples were analyzed for BuChE activity using the Ellman’s assay. The incubation times of plasma and anti-BuChE antibodies marginally affected the extraction efficiency of BuChE whereas a decrease in plasma volume increased the extraction efficiency. Cross-linking of anti-BuChE antibodies on agarose increased the extraction efficiency. The NAb protein-G Spin Kit can be used successfully to extract BuChE from human plasma. This extraction technique may be coupled to downstream analytical analyses for diagnosing exposure to OP compounds.

Dihydroergotamine mesylate-loaded dissolving microneedle patch made of polyvinylpyrrolidone for management of acute migraine therapy

Journal of Controlled Release

Abstract Migraine is a widespread neurological disease with negative effects on quality of life and productivity. Moderate to severe acute migraine attacks can be treated with dihydroergotamine mesylate (DHE), an ergot derivative that is especially effective in non-responders to triptan derivatives. To overcome limitations of current DHE formulations in subcutaneous injection and nasal spray such as pain, adverse side effects and poor bioavailability, a new approach is needed for DHE delivery enabling painless self-administration, quick onset of action, and high bioavailability. In this study, we developed a dissolving microneedle patch (MNP) made of polyvinylpyrrolidone, due to its high aqueous solubility and solubility enhancement properties, using a MNP design previously shown to be painless and simple to administer. DHE-loaded MNPs were shown to have a content uniformity of 108±9% with sufficient mechanical strength for insertion to pig skin ex vivo and dissolution within 2min. In vivo pharmacokinetic studies were carried out on hairless rats, and DHE plasma levels were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The area under curve (AUC) value after DHE delivery by MNP (1259±917ng/mL min) was not significantly different (p>0.05) as compared to subcutaneous injection, with a relative bioavailability of 97%. Also, appreciable plasma levels of DHE were seen within 5min for both delivery methods and tmax value of MNPs (38±23min) showed no significant difference (p>0.05) compared to subcutaneous injection (24±13min). These results suggest that DHE-loaded MNPs have promise as an alternative DHE delivery method that can be painlessly self-administered with rapid onset and high bioavailability.

Monitoring drug pharmacokinetics and immunologic biomarkers in dermal interstitial fluid using a microneedle patch

Biomedical Microdevices

Minimally invasive point-of-care diagnostic devices are of great interest for rapid detection of biomarkers in diverse settings. Although blood is the most common source of biomarkers, interstitial fluid (ISF) is an alternate body fluid that does not clot or contain red blood cells that often complicate analysis. However, ISF is difficult to collect. In this study, we assessed the utility of a microneedle patch to sample microliter volumes of ISF in a simple and minimally invasive manner. We demonstrated the use of ISF collected in this way for therapeutic drug monitoring by showing similar vancomycin pharmacokinetic profiles in ISF and serum from rats. We also measured polio-specific neutralizing antibodies and anti-polio IgG in ISF similar to serum in rats immunized with polio vaccine. These studies demonstrate the potential utility of ISF collected by microneedle patch in therapeutic drug monitoring and immunodiagnostic applications.

Development of a solid phase extraction method to extract Gonyautoxins from urine

Journal of Drug Development and Clinical Trials

Saxitoxin (STX), Neosaxitoxin (NEO) and Gonyautoxins (GTXs) I-IV form a carbamate subgroup of hydrophilic Paralytic Shellfish Toxins (PSTs) that can be found in shellfish that have fed upon red tide algae. Analytical methods to detect these toxins have been developed primarily for the analysis of contaminated shellfish. Diagnostic tests for measuring exposure to these toxins is limited to a single urinalysis method for STX and NEO and is confirmed by analysis of unconsumed shellfish. Validated diagnostic methods to measure exposure to GTXs from urine do not exist and are needed for accurate diagnosis of paralytic shellfish poisoning. Here we describe solid phase extraction (SPE) approaches to extract GTXs from urine in an effort to develop an analytical diagnostic method for GTX exposure. Three SPE sorbents have been explored in this study: mixedmode strong cationic exchange.weak cationic exchange, and mixed-mode weak anionic exchange. No toxins were recovered from weak anion exchange extractions. Weak cationic exchange shows higher recoveries for GTXs than strong cationic exchange and may be useful for measuring high-level exposures. However, extraction efficiencies are low due to urine matrix effects on the extraction and future improvements on the method are needed for measuring low-level exposures.

Commentary on Health and Environmental Risks from Hydraulic Fracturing

Hydraulic Fracturing Impacts and Technologies: A Multidisciplinary Perspective. CRC Press, Boca Raton

Petrochemical production has been happening in the United States since the 1900s.1 In the United States, total oil production had been declining for decades as shown in Figure 5.1. With the rise in oil prices, unconventional oil is now being recovered in everincreasing quantities. The International Energy Agency has dened unconventional oil as hydrocarbons that must be obtained using nontraditional technologies, which include hydraulic fracturing. Figure 5.2 presents the thousands of barrels produced per day from January 2000 through May 2011, highlighting the increase in tight oil production in the United States in recent years.

Cleaning and disinfecting environmental surfaces in health care: Toward an integrated framework for infection and occupational illness prevention

American Journal of Infection Control

BACKGROUND: The Cleaning and Disinfecting in Healthcare Working Group of the National Institute for Occupational Safety and Health, National Occupational Research Agenda, is a collaboration of infection prevention and occupational health researchers and practitioners with the objective of providing a more integrated approach to effective environmental surface cleaning and disinfection (C&D) while protecting the respiratory health of health care personnel. METHODS: The Working Group, comprised of >40 members from 4 countries, reviewed current knowledge and identified knowledge gaps and future needs for research and practice. RESULTS: An integrated framework was developed to guide more comprehensive efforts to minimize harmful C&D exposures without reducing the effectiveness of infection prevention. Gaps in basic knowledge and practice that are barriers to an integrated approach were grouped in 2 broad areas related to the need for improved understanding of the (1) effectiveness of environmental surface C&D to reduce the incidence of infectious diseases and colonization in health care workers and patients and (2) adverse health impacts of C&D on health care workers and patients. Specific needs identified within each area relate to basic knowledge, improved selection and use of products and practices, effective hazard communication and training, and safer alternatives. CONCLUSION: A more integrated approach can support multidisciplinary teams with the capacity to maximize effective and safe C&D in health care.

Chemical Weapons Use in Jebel Marra – Analysis of Symptoms and Potential Agents Used

Public Interest Report, Federation of American Scientists

Case diagnosis and characterization of suspected paralytic shellfish poisoning in Alaska

Harmful Algae

Clinical cases of paralytic shellfish poisoning (PSP) are common in Alaska, and result from human consumption of shellfish contaminated with saxitoxin (STX) and its analogues. Diagnosis of PSP is presumptive and based on recent ingestion of shellfish and presence of manifestations consistent with symptoms of PSP; diagnosis is confirmed by detection of paralytic shellfish toxins in a clinical specimen or food sample. A clinical diagnostic analytical method using high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) was used to evaluate the diagnosis of saxitoxin-induced PSP (STX-PSP) in 11 Alaskan patients using urine specimens collected between June 2010 and November 2011. Concentrations of urinary STX were corrected for creatinine concentrations to account for dilution or concentration of urine from water intake or restriction, respectively. Of the 11 patients with suspected PSP, four patients were confirmed to have STX-PSP by urine testing (24-364ng STX/g creatinine). Five patients had clinical manifestations of PSP though no STX was detected in their urine. Two patients were ruled out for STX-PSP based on non-detected urinary STX and the absence of clinical findings. Results revealed that dysphagia and dysarthria may be stronger indicators of PSP than paresthesia and nausea, which are commonly used to clinically diagnose patients with PSP. PSP can also occur from exposure to a number of STX congeners, such as gonyautoxins, however their presence in urine was not assessed in this investigation. In addition, meal remnants obtained from six presumptive PSP cases were analyzed using the Association of Official Analytical Chemists' mouse bioassay. All six samples tested positive for PSP toxins. In the future, the clinical diagnostic method can be used in conjunction with the mouse bioassay or HPLC-MS/MS to assess the extent of STX-PSP in Alaska where it has been suggested that PSP is underreported.

Quantitative analysis and stability of the rodenticide TETS (tetramine) in finished tap water

Analytical Methods

The determination of the rodenticide tetramethylenedisulfotetramine (TETS) in drinking water is reportable through the use of automated sample preparation via solid phase extraction and detection using isotope dilution gas chromatography-mass spectrometry. The method was characterized over twenty-two analytical batches with quality control samples. Accuracies for low and high concentration quality control pools were 100 and 101%, respectively. The minimum reporting level (MRL) for TETS in this method is 0.50 μg L−1. Five drinking waters representing a range of water quality parameters and disinfection practices were fortified with TETS at ten times the MRL and analyzed over a 28 day period to determine the stability of TETS in these waters. The amount of TETS measured in these samples averaged 100 ± 6% of the amount fortified suggesting that tap water samples may be held for up to 28 days prior to analysis.

Method Development for Extraction of Butyrylcholinesterase Using Protein-G Agarose Spin Columns

Journal of Applied Bioanalysis

Butyrylcholinesterase (BuChE) is a biomarker of organophosphate (OP) poisoning and can be used as a diagnostic marker to measure exposure to OP compounds. The purpose of this study was to develop a method to extract BuChE from human plasma. BuChE was extracted from plasma using the NAb protein-G Agarose Spin Kit. Factors affecting extraction like incubation time, plasma volume and cross-linking of antibodies to agarose beads were evaluated. All samples were analyzed for BuChE activity using the Ellman’s assay. The incubation times of plasma and anti-BuChE antibodies marginally affected the extraction efficiency of BuChE whereas a decrease in plasma volume increased the extraction efficiency. Cross-linking of anti-BuChE antibodies on agarose increased the extraction efficiency. The NAb protein-G Spin Kit can be used successfully to extract BuChE from human plasma. This extraction technique may be coupled to downstream analytical analyses for diagnosing exposure to OP compounds.

Dihydroergotamine mesylate-loaded dissolving microneedle patch made of polyvinylpyrrolidone for management of acute migraine therapy

Journal of Controlled Release

Abstract Migraine is a widespread neurological disease with negative effects on quality of life and productivity. Moderate to severe acute migraine attacks can be treated with dihydroergotamine mesylate (DHE), an ergot derivative that is especially effective in non-responders to triptan derivatives. To overcome limitations of current DHE formulations in subcutaneous injection and nasal spray such as pain, adverse side effects and poor bioavailability, a new approach is needed for DHE delivery enabling painless self-administration, quick onset of action, and high bioavailability. In this study, we developed a dissolving microneedle patch (MNP) made of polyvinylpyrrolidone, due to its high aqueous solubility and solubility enhancement properties, using a MNP design previously shown to be painless and simple to administer. DHE-loaded MNPs were shown to have a content uniformity of 108±9% with sufficient mechanical strength for insertion to pig skin ex vivo and dissolution within 2min. In vivo pharmacokinetic studies were carried out on hairless rats, and DHE plasma levels were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The area under curve (AUC) value after DHE delivery by MNP (1259±917ng/mL min) was not significantly different (p>0.05) as compared to subcutaneous injection, with a relative bioavailability of 97%. Also, appreciable plasma levels of DHE were seen within 5min for both delivery methods and tmax value of MNPs (38±23min) showed no significant difference (p>0.05) compared to subcutaneous injection (24±13min). These results suggest that DHE-loaded MNPs have promise as an alternative DHE delivery method that can be painlessly self-administered with rapid onset and high bioavailability.

Monitoring drug pharmacokinetics and immunologic biomarkers in dermal interstitial fluid using a microneedle patch

Biomedical Microdevices

Minimally invasive point-of-care diagnostic devices are of great interest for rapid detection of biomarkers in diverse settings. Although blood is the most common source of biomarkers, interstitial fluid (ISF) is an alternate body fluid that does not clot or contain red blood cells that often complicate analysis. However, ISF is difficult to collect. In this study, we assessed the utility of a microneedle patch to sample microliter volumes of ISF in a simple and minimally invasive manner. We demonstrated the use of ISF collected in this way for therapeutic drug monitoring by showing similar vancomycin pharmacokinetic profiles in ISF and serum from rats. We also measured polio-specific neutralizing antibodies and anti-polio IgG in ISF similar to serum in rats immunized with polio vaccine. These studies demonstrate the potential utility of ISF collected by microneedle patch in therapeutic drug monitoring and immunodiagnostic applications.

Development of a solid phase extraction method to extract Gonyautoxins from urine

Journal of Drug Development and Clinical Trials

Saxitoxin (STX), Neosaxitoxin (NEO) and Gonyautoxins (GTXs) I-IV form a carbamate subgroup of hydrophilic Paralytic Shellfish Toxins (PSTs) that can be found in shellfish that have fed upon red tide algae. Analytical methods to detect these toxins have been developed primarily for the analysis of contaminated shellfish. Diagnostic tests for measuring exposure to these toxins is limited to a single urinalysis method for STX and NEO and is confirmed by analysis of unconsumed shellfish. Validated diagnostic methods to measure exposure to GTXs from urine do not exist and are needed for accurate diagnosis of paralytic shellfish poisoning. Here we describe solid phase extraction (SPE) approaches to extract GTXs from urine in an effort to develop an analytical diagnostic method for GTX exposure. Three SPE sorbents have been explored in this study: mixedmode strong cationic exchange.weak cationic exchange, and mixed-mode weak anionic exchange. No toxins were recovered from weak anion exchange extractions. Weak cationic exchange shows higher recoveries for GTXs than strong cationic exchange and may be useful for measuring high-level exposures. However, extraction efficiencies are low due to urine matrix effects on the extraction and future improvements on the method are needed for measuring low-level exposures.

Rapid and Sensitive ELISA Screening Assay for Several Paralytic Shellfish Toxins in Human Urine

Journal of Analytical Toxicology

Paralytic shellfish poisoning is caused by a group of paralytic shellfish toxins that are produced by dinoflagellates. Toxins in this group include saxitoxin, neosaxitoxin and gonyautoxins. A rapid diagnostic test to identify poisoning by these toxins can be helpful in guiding the appropriate treatment of victims. Additionally, quick receipt of diagnostic results can provide timely proof that shellfish harvesting should be stopped in a given area, thereby preventing additional exposures. We have developed and validated a rapid urinary enzyme-linked immunosorbent assay-based screening test to diagnose exposure to several major paralytic shellfish toxins. The lower limit of detection (LLOD) for multiple paralytic shellfish toxins was characterized as 0.02, 0.10, 0.10, 1.0, 1.0 and 15 ng/mL for saxitoxin, gonyautoxin 2,3, decarbamoyl gonyautoxin 2,3, decarbamoyl saxitoxin, neosaxitoxin and gonyautoxin 1,4, respectively. No interferences were identified in unspiked pooled urine or in specimens collected from unexposed individuals indicating that this method is specific for the paralytic shellfish toxins tested. The accuracy of this test was demonstrated in 10 individual urine specimens with osmolalities ranging from 217 to 1,063 mOsmol/kg and pHs ranging between 5.06 and 7.45. These specimens were spiked with toxins at their LLODs and the presence of toxins at these concentrations was accurately identified in all cases. These results indicate that this diagnostic test can be used to rapidly and accurately screen urine for paralytic shellfish toxins.