Ruth E. Winecker

Detection of Cocaine and Its Metabolites in Breast Milk

A method was developed for measuring cocaine and its metabolites, benzoylecgonine, ecgonine methyl ester, norcocaine, ecgonine ethyl ester, cocaethylene, and m-hydroxybenzoylecgonine, in breast milk by gas chromatography/mass spectrometry. Limits of detection for this method ranged from 2.5 to 10 ng/mL, and limits of quantitation ranged from 5 to 50 ng/mL. For each of the compounds measured by this method, linear response was demonstrated to 750 ng/mL. Breast milk was collected from 11 mothers who admitted to drug use during pregnancy and ten drug-free volunteers serving as control subjects. Cocaine was detected in six of the specimens obtained from drug-exposed subjects, and in none of the drug-free control subjects. In breast milk specimens where cocaine and one or more of its metabolites were detected, the concentration of parent compound was greater than any of the metabolites. The highest cocaine concentration found was over 12 microg/mL. Breast-fed infants of cocaine abusing mothers may be exposed to significant amounts of drug orally.

HbA1c as a Postmortem Tool to Identify Glycemic Control

Estimates suggest that more than 5A million U.S. citizens unknowingly have diabetes and are at increased risk of morbidity and mortality. We evaluated an immunoturbidimetric measurement of glycated hemoglobin (%HbA1c) as a postmortem tool to identify such individuals. Although postmortem samples undergo some degradation, the effects are not sufficient to invalidate the use of the test or method. Using two study populations whose medical history of diabetes was known, we found the mean %HbA1c of the non-diabetics (5.8+/-0.3) to be statistically different from that of the diabetics (12.4+/-2.8). For the population whose disease status was unknown, the %HbA1c ranged from 4.7 to 16.8. For six unknowns whose values exceeded 7.0%. the mean was 11.7%, which did not differ statistically from the diabetic mean (p = 0.6615). These studies suggest that postmortem blood samples can be used to characterize HbA1c values.

Unusual fentanyl patch administration.

Fentanyl is an extremely potent narcotic analgesic that is becoming more popular as a drug of abuse. Because of the unique way in which the drug is packaged and delivered, the potential for unusual methods of abuse exists. We report the first case of true fentanyl patch ingestion in the medical literature. Initially, though unusual, cases of fentanyl ingestion were thought to have been reported, but further investigation of the literature revealed that in other case reports the patches had been held in the mouth and chewed. Because no reports of swallowing the patch had been published, suicide was initially a strong consideration in this case; however, further investigation showed that the decedent and his brother enjoyed swallowing the patches for quick “highs.” Cases such as these serve to remind medical examiners and law enforcement officials of the value of performing thorough death investigations by performing complete autopsies with toxicological testing and correlating with investigation information to form an opinion with regard to the cause and manner of death.

Quantification of Antidepressants Using Gas Chromatography-Mass Spectrometry

Antidepressants are of great interest to clinical and forensic toxicologists as they are frequently used in suicidal gestures; they can be the source of drug interactions and some have narrow therapeutic indices making the potential for toxicity more likely. There are five categories of antidepressants based on function and/or structure. These are monoamine oxidase inhibitors (MAOI), cyclic antidepressants including tricyclic and tetracyclic compounds (TCA), selective serotonin reuptake inhibitors (SSRI), serotonin-norepinephrine reuptake inhibitors (SNRI), and atypical compounds. This method is designed to detect the presence of antidepressant drugs in blood/serum, urine, and tissue specimens using gas chromatography/mass spectrometry (GC/MS) following liquid-liquid extraction (LLE) and identified by relative retention times and mass spectra.

New Insights into an Old Poison, Arsenic

CE update [generalist] New Insights into an Old Poison, Arsenic Catherine A. Hammett-Stabler, PhD, DABCC, FACB,1 Larry A. Broussard, PhD, DABCC, FACB,2 Ruth E. Winecker, PhD,3,1 Jeri D. Ropero-Miller, PhD3,1 1Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, NC, 2LSU Health Sciences Center, Clinical Laboratory Sciences, New Orleans, LA, 3Office of the Chief Medical Examiner, State of North Carolina, Chapel Hill, NC

Postmortem Metaxalone (Skelaxin®) Data from North Carolina

The North Carolina Office of the Chief Medical Examiner Toxicology Laboratory identified 61 cases from 2002 to 2014 where metaxalone was detected during routine postmortem drug screening in support of a determination of cause and manner of death. Decedents were divided into groups based on the manner of death with the goal of studying metaxalone concentrations in overdose and non-overdose situations (natural, accident, suicide and undetermined). Subgroups were established for cases in which metaxalone contributed to the cause of death (attributed) and cases in which it did not (unattributed). Attributed cases were divided into those where metaxalone additively combined with other drugs and cases in which the drug was present in sufficient amounts to be the primary cause of death, regardless of other drugs present and the concentrations of those drugs. The mean metaxalone concentration for the additive deaths was 14.2 mg/L with a median value of 11 mg/L (n = 18) and a mean metaxalone concentration of 36.7 mg/L with a median value of 32 mg/L (n = 9) for primary deaths. For unattributed metaxalone concentrations, the mean was 3.4 mg/L with a median value of 2.9 mg/L (n = 31). Of the 61 cases, 34% fall at or below a therapeutic concentration of ≤4 mg/L. The selected case studies offer valuable information regarding postmortem interpretation.

Postmortem Levetiracetam (Keppra) Data from North Carolina

Levetiracetam (Keppra®) is one of the newer anticonvulsant drugs used to treat seizures. Since 2003, the North Carolina Office of the Chief Medical Examiner Toxicology Laboratory has collected quantitative levetiracetam data in samples for 56 postmortem cases. The data presented herein will provide the forensic community with concentrations to assist in the interpretation of levetiracetam in postmortem blood. Decedents were divided into two groups according to manner of death as determined by the medical examiner for the purposes of studying levetiracetam concentrations. There were equal numbers of natural (N = 28) and non-natural deaths (N = 28). These data were subsequently divided into subgroups for further study to explore the therapeutic range of levetiracetam and how it relates to postmortem data. The cases not certified as natural were investigated to study levetiracetam concentrations in cases where it was determined to contribute to the cause of death (attributed) and those where it was not (unattributed). Until now, the literature has only reported levetiracetam overdoses in which the individuals have recovered with respiratory support. Discussed are two suicidal drug deaths from 2010 that are noted to have elevated levels of levetiracetam, 190 and 35 mg/L. Also included in the complete data set are postmortem concentrations for five patients under the age of 10 with levetiracetam ranging from 1.4 to 50 mg/L. This paper will also address the adverse effects of the drug and explore its potential risk for suicide.

Chromatographic methods in clinical chemistry and toxicology

Preface. List of Contributors. 1. Quality Assurance, Quality Control and Method Validation in Chromatographic Applications (Michele L. Merves and Bruce A. Goldberger). 1.1 Introduction. 1.2 History. 1.3 Definition of Quality Assurance and Quality Control. 1.4 Professional Organizations. 1.5 Internal Quality Assurance and Control. 1.6 External Quality Assurance. References. 2. Liquid Chromatographic-Mass Spectrometric Measurement of Anabolic Steroids (Don H. Catlin, Yu-Chen Chang, Borislav Starcevic and Caroline K. Hatton). 2.1 Introduction. 2.2 LC-MS Analysis of Synthetic Steroids or Animal Samples. 2.3 LC-MS Analysis of Natural Androgens in Human Samples. 2.4 Conclusion. References. 3. High-performance Liquid Chromatography in the Analysis of Active Ingredients in Herbal Nutritional Supplements (Amitava Dasgupta). 3.1 Introduction. 3.2 St JohnaAAs Wort. 3.3 Herbal Supplements with Digoxin-like Immunoreactivity. 3.4 Herbal Remedies and Abnormal Liver Function Tests. 3.5 Ginkgo Biloba. 3.6 Echinacea. 3.7 Valerian. 3.8 Feverfew. 3.9 Garlic. 3.10 Ephedra (Ma Huang) and Related Drugs. 3.11 Conclusions. References. 4. Measurement of Plasma L-DOPA and L-Tyrosine by High-Performance Liquid Chromatography as a Tumor Marker in Melanoma (Thierry Le Bricon, Sabine Letellier, Konstantin Stoitchkov and Jean-Pierre Garnier). 4.1 Introduction. 4.2 Melanogenesis. 4.3 L-DOPA Alone. 4.4 L-DOPA/L-Tyrosine Ratio. 4.5 Conclusion. References. 5. Hypersensitive Measurement of Proteins by Capillary Isoelectric Focusing and Liquid Chromatography-Mass Spectrometry (Feng Zhou and Murray Johnston). 5.1 Introduction. 5.2 A Robust CIEF-RPLC Interface. 5.3 First-Generation CIEF-RPLC-MS System for Proteins. 5.4 Second-Generation CIEF-RPLC-MS System. 5.5 Future Improvements. Acknowledgment. References. 6. Chromatographic Measurement of Transferrin Glycoforms for Detecting Alcohol Abuse and Congenital Disorders of Glycosylation (Anders Helander). 6.1 Introduction. 6.2 Transferrin Microheterogeneity. 6.3 Carbohydrate-deficient Transferrin (CDT). 6.4 Congenital Disorders of Glycosylation (CDG). 6.5 Analytical Methods for Transferrin Microheterogeneity. 6.6 Chromatographic Methods for CDT. 6.7 Chromatographic Methods for CDG. 6.8 Summary and Conclusions. References. 7. Chromatographic Measurements of Catecholamines and Metanephrines (Eric C. Y. Chan and Paul C. L. Ho). 7.1 Background. 7.2 Analytical Measurements of Catecholamines and Metanephrines. 7.3 Early Methods. 7.4 Current Chromatographic Methods. 7.5 Practical Considerations for the Stability of Urinary Catecholamines and Metanephrines During Storage. 7.6 Future Developments. Dedication. References. 8. Chromatographic Measurement of Volatile Organic Compounds (VOCs) (Larry A. Broussard). 8.1 Introduction. 8.2 General Considerations. 8.3 Intended Use. 8.4 Volatility of Compounds. 8.5 Sample Collection, Handling and Storage. 8.6 Headspace Gas Chromatographic Methods. 8.7 Columns and Detectors. 8.8 Identification, Quantitation and Confirmation. 8.9 Ethanol and Other Volatile Alcohols. 8.10 Inhalants and Screening for Multiple VOCs. 8.11 Interpretation. 8.12 Conclusion. References. 9. Chromatographic Techniques for Measuring Organophosphorus Pesticides (H. Wollersen and F. Musshoff). 9.1 Introduction. 9.2 Organophosphorus Pesticides (OPs). 9.3 Conclusion. References. 10. Chromatographic Analysis of Nerve Agents (Jeri D. Ropero-Miller). 10.1 Introduction. 10.2 Neuromuscular Blockers. 10.3 Paralytic Shellfish Poisoning: Saxitoxin. 10.4 Summary. References. 11. History and Pharmacology of c-Hydroxybutyric Acid (Laureen Marinetti). 11.1 Introduction. 11.2 History of Illicit Use of GHB. 11.3 Clinical Use of GHB in Humans. 11.4 History of Illicit Use of GBL and 1,4BD. 11.5 Distribution and Pharmacokinetics of GHB, GBL and 1,4BD. 11.6 GHB Interpretation Issues and Post-mortem Production. 11.7 Analysis for GHB, GBL and 1,4BD. References. 12. Liquid Chromatography with Inductively Coupled Plasma Mass Spectrometric Detection for Element Speciation: Clinical and Toxicological Applications (Katarzyna Wrobel, Kazimierz Wrobel and Joseph A. Caruso). 12.1 Introduction. 12.2 Liquid Chromatography with Inductively Coupled Plasma Mass Spectrometric Detection. 12.3 Analytical Applications of Clinical and Toxicological Relevance. 12.4 Conclusions and Future Trends. 12.5 Abbreviations. References. 13. Applications of Gas Chromatography-Mass Spectrometry to the Determination of Toxic Metals (Suresh K. Aggarwal, Robert L. Fitzgerald and David A. Herold). 13.1 Introduction. 13.2 Instrumentation. 13.3 Experimental Procedure. 13.4 GC-MS Studies. 13.5 Conclusions. References. Index..

Prevalence of gabapentin in drug overdose postmortem toxicology testing results

BACKGROUND The goal of this study was to establish and compare baseline data on the prevalence of gabapentin identified through postmortem toxicology testing among drug overdose decedents in several geographically diverse states/jurisdictions with differing levels of drug overdose fatality burdens in 2015. METHODS Death certificates and postmortem toxicology result reports from five U.S. jurisdictions were used to identify residents who died from drug overdoses in year 2015 and to calculate prevalence rates of gabapentin in postmortem toxicology by jurisdiction. RESULTS On average, 22% of all drug overdose decedents in our study tested positive for gabapentin. The percentage of gabapentin-positive overdose deaths varied significantly among jurisdictions: 4% in Northeast Tennessee, 7% in Maricopa County, 15% in West Virginia, 20% in North Carolina, and 41% in Kentucky (p < 0.0001). Among the drug overdose decedents who tested positive for opioids (including heroin), 26% also tested positive for gabapentin, with significant variation among states/jurisdictions (p < 0.0001). There was a significant difference in the gender distribution among drug overdose decedents who tested positive for gabapentin (46% male) vs. those who tested negative for gabapentin (65% male) (p < 0.0001). In Kentucky, gabapentin was listed as a contributing drug on the death certificate in 40% of the overdose deaths with gabapentin-positive toxicology; in North Carolina this percentage was 57%. CONCLUSIONS Routine gabapentin postmortem testing and linking of death certificate, medical examiner, coroner, toxicology, and prescription history data will provide more reliable information on the extent of gabapentin misuse, diversion, and implications for clinical care.