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3,4-Methylenedioxypyrovalerone (MDPV) is a psychoactive, synthetic analog of the central nervous system stimulant cathinone. Its recent popularity as a recreational drug in the United States has led to numerous reports to poison control centers across the country. As with other synthetic cathinones, the recreational use of MDPV has resulted in death. MDPV is thought to exert its pharmacologic effects by inhibiting the reuptake of dopamine and norepinephrine. This report describes the case of an exposure of a 39-year-old male to MDPV, which resulted in his death. Postmortem concentrations of MDPV in various tissues were measured. The detection of MDPV in tissues and fluids was accomplished using gas chromatography-mass spectrometry analysis after solid-phase extraction. Blood analysis also demonstrated therapeutic levels of lamotrigine, fluoxetine, risperidone, benztropine, pseudoephedrine and ibuprofen. The detection of cathinones in hair was conducted using high-performance liquid chromatography-tandem mass spectrometry after solid-phase extraction. MDPV was uniformly distributed among multiple tissues (blood, brain, muscle, cerebrospinal fluid and lung) at concentrations of approximately 0.4 to 0.6 µg/mL. Tissue and fluids responsible for detoxification/excretion had higher concentrations of MDPV (kidney, liver and bile > 0.8 µg/mL). A blood concentration ≥ 0.4 µg/mL was judged sufficient to cause death. The cause of death was ruled MDPV intoxication resulting in cardiac arrhythmia.

Postmortem toenail samples were used for the detection of cocaine (COC), benzoylecgonine (BZE), norcocaine (NCOC), cocaethylene (CE), morphine (MOR), 6-monoacetylmorphine (6-MAM), codeine (COD), and hydrocodone (HDC). After the toenail clippings were washed with methanol, they were solubilized in 0.1 M potassium phosphate (pH 5.0). The drugs of interest, along with internal standards, were isolated by solid-phase extraction followed by derivatization with N-methyl-N-trimethylsilyl-trifluoroacetamide. The derivatized products were analyzed by gas chromatography-mass spectrometry operated in the selective ion monitoring (SIM) mode. The limit of quantitation for all analytes was 0.3 ng on column. The quantities of drugs found in toenails of each of 46 decedents were compared with those of their corresponding postmortem fluids. The toenails of the 46 decedents were tested for COC, BZE, NCOC, and CE, and 34 of the collected samples were also tested for opiates. COC and BZE concentrations ranged from 0.20 to 140.17 (n = 20) and 0.30 to 315.44 ng/mg (n = 21), respectively. NCOC concentrations of 6.78 and 0.66 ng/mg and CE concentrations of 2.60 and 0.73 ng/mg were detected in two of the decedents' toenails. MOR and 6-MAM were detected in three sets of toenails at average concentrations of 0.37 and 0.89 ng/mg, respectively. COD was detected in two sets of specimens at concentrations of 3.07 and 1.02 ng/mg. HDC (0.62 ng/mg) was found in only one set of specimens.

Postmortem fingernail and toenail specimens were utilized for the detection of cocaine analytes and opiates. Nail clippings were obtained from suspected overdoses and/or drug users. Nail clippings were washed with methanol and then solubilized in 0.1M potassium phosphate (pH 5.0). Analytes were isolated from the solubilized nails and methanolic washes by solid-phase or liquid-liquid extraction techniques. Quantitation was performed by gas chromatography-mass spectrometry. Clippings from each hand and foot were analyzed separately for comparison purposes. Concentrations of all the analytes were significantly higher in fingernails than in toenails. Cocaine analytes were detected in the nails of 15 cases with the following concentration ranges (ng/mg): cocaine (n = 15) 1.2-414.1; benzoylecgonine (n = 15) 1.4-170.3; ecgonine methyl ester (n = 14) 0.19-27.0; norcocaine (n = 12) 0.11-32.7; cocaethylene (n = 2) 0.08-2.93. Opiates were detected in 17 cases with the following concentration ranges (ng/mg): morphine (n = 15) 0.05-407.9; 6-acetylmorphine (n = 15) 0.04-504.0; codeine (n = 9) 0.06-8.84; hydromorphone (n = 4) 0.02-0.45. Oxycodone and hydrocodone were each detected in one case. The extent of drug incorporation due to external contamination was evaluated by comparing the differences in the amount of drugs detected in fingernails and toenails, along with the corresponding washes of those nails. These results demonstrate the usefulness of nails as postmortem specimens in detecting drugs of abuse.

The concentration of drugs and metabolites in cerebrospinal fluid (CSF) and blood were determined in 282 autopsied cases using liquid-liquid extraction techniques and gas chromatographic analyses. All drugs were confirmed in one matrix by gas chromatography-mass spectrometry. CSF/blood ratios were used to compare the two biological fluids. Classes of drugs evaluated in this study included: benzodiazepines, anticonvulsants, sedatives, opioids, antidepressants, anesthetics, and antihistamines. The majority of the drugs tested were readily detected in CSF specimens. The average CSF/blood ratio for most drugs was in the range of 0.05-0.50. Interpretation of these results is difficult because protein binding, half-life, hydrophobic properties, and pKa of a drug, in addition to survival time after drug use, influence the CSF/blood ratio. While CSF specimens do provide a viable alternative testing matrix when blood specimens are not available, they should not be used to estimate blood drug concentrations.

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