Analysis of extensively washed hair from cocaine users and drug chemists to establish new reporting criteria.

Samples from a self-proclaimed cocaine (COC) user, from 19 drug users (postmortem) and from 27 drug chemists were extensively washed and analyzed for COC, benzoylecgonine, norcocaine (NC), cocaethylene (CE) and aryl hydroxycocaines by liquid chromatography-tandem mass spectrometry. Published wash criteria and cutoffs were applied to the results. Additionally, the data were used to formulate new reporting criteria and interpretation guidelines for forensic casework. Applying the wash and reporting criteria, hair that was externally contaminated with COC was distinguished from hair collected from individuals known to have consumed COC. In addition, CE, NC and hydroxycocaine metabolites were only present in COC users' hair and not in drug chemists' hair. When properly applied, the use of an extended wash, along with the reporting criteria defined here, will exclude false-positive results from environmental contact with COC.

Benzodiazepines and metabolites from biological fluids by liquid chromatography electrospray tandem mass spectrometry.

Solid-phase extraction and liquid chromatography-tandem mass spectrometry are invaluable techniques for the determination of benzodiazepines and metabolites in biological matrices. The reason for using tandem mass spectrometry is to increase limits of detection without the need for chemical derivatization. Here we describe a technique for the detection of 26 benzodiazepines and metabolites at a detection limit of approximately 1-2 ng/mL in blood and 1-5 ng/mL in urine when screened using a data-dependent scan method.

Ethanol analysis from biological samples by dual rail robotic autosampler.

Detection, identification, and quantitation of ethanol and other low molecular weight volatile compounds in liquid matrices by headspace gas chromatography-flame ionization detection (HS-GC-FID) and headspace gas chromatography-mass spectrometry (HS-GC-MS) are becoming commonly used practices in forensic laboratories. Although it is one of the most frequently utilized procedures, sample preparation is usually done manually. Implementing the use of a dual-rail, programmable autosampler can minimize many of the manual steps in sample preparation. The autosampler is configured so that one rail is used for sample preparation and the other rail is used as a traditional autosampler for sample introduction into the gas chromatograph inlet. The sample preparation rail draws up and sequentially adds a saturated sodium chloride solution and internal standard (0.08%, w/v acetonitrile) to a headspace vial containing a biological sample, a calibrator, or a control. Then, the analytical rail moves the sample to the agitator for incubation, followed by sampling of the headspace for analysis. Using DB-624 capillary columns, the method was validated on a GC-FID and confirmed with a GC-MS. The analytes (ethanol, acetonitrile) and possible interferences (acetaldehyde, methanol, pentane, diethyl ether, acetone, isopropanol, methylene chloride, n-propanol, and isovaleraldehyde) were baseline resolved for both the GC-FID and GC-MS methods. This method demonstrated acceptable linearity from 0 to 1500 mg/dL. The lower limit of quantitation (LOQ) was determined to be 17 mg/dL and the limit of detection was 5 mg/dL.

Rapid quantification of urinary 11-nor-delta9-tetrahydrocannabinol-9-carboxylic acid using fast gas chromatography-mass spectrometry.

Human urine specimens that were determined to be presumptively positive for metabolites of delta9-tetrahydrocannabinol by immunoassay screening were assayed using a novel fast gas chromatography-mass spectrometry (FGC-MS) analytical method to determine whether this method would improve the efficiency of specimen processing without diminishing the reliability of metabolite identification and quantification. Urine specimens were spiked with deuterated internal standard, subjected to solid-phase extraction, and derivatized using tetramethylammonium hydroxide and iodomethane. The methyl ester/methyl ether derivatives were identified and quantified using both a traditional GC-MS method and the newly developed FGC-MS method. The FGC-MS method was demonstrated to be linear between 3.8 and 1500 ng/mL 11-nor-delta9-tetrahydrocannabinol-9-carboxylic acid (11-nor-delta-THC-COOH). The intrarun precision of 15 replicates of a 15 ng/mL control and the interrun precision of 161 sets of 7, 15, and 60 ng/mL controls were acceptable (coefficients of variation < 5.5%). The FGC-MS method was demonstrated to be specific for identifying 11-nor-delta9-THC-COOH and none of 43 tested substances interfered with identification and quantification of 11-nor-delta9-THC-COOH. Excellent data concordance (R2 > 0.993) was found for two specimen sets assayed using both methods. The FGC-MS method, when compared with a traditional GC-MS method, reduces total assay time by approximately 40% with no decrease in data quality.

Rapid simultaneous determination of amphetamine, methamphetamine, 3,4-methylenedioxyamphetamine, 3,4-methylenedioxymethamphetamine, and 3,4-methylenedioxyethylamphetamine in urine by fast gas chromatography-mass spectrometry.

The use of fast gas chromatography-mass spectrometry (FGC-MS) was investigated to improve the efficiency of analysis of urine specimens that previously screened presumptively positive for amphetamine (AMP), methamphetamine (MAMP), 3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxymethamphetamine (MDMA), and/or 3,4 methylenedioxyethylamphetamine (MDEA) by immunoassay testing. Specimens were pretreated with basic sodium periodate, extracted using a positive-pressure manifold/cation-exchange solid-phase cartridge methodology, and derivatized using 4-carbethoxyhexafluorobutyryl chloride (4-CB). The analytical method was compared to traditional GC-MS analysis and evaluated with respect to assay chromatography, linearity, sensitivity, precision, accuracy, and reproducibility. The limits of detection were 62.5 ng/mL for MDA and 31.25 ng/mL for AMP, MAMP, MDMA, and MDEA. All of the target analytes were linear to 12,000 ng/mL with the exception of MAMP which was linear to 10,000 ng/mL. The intra-assay precision of a 500 ng/mL multiconstituent control (n=15) ranged from 522.6 to 575.9 ng/mL with a coefficient of variation of less than 3.8%. Authentic human urine specimens (n=187) previously determined to contain the target analytes were re-extracted and analyzed by both FGC-MS and the currently utilized GC-MS method. No significant differences in specimen concentration were observed between these analytical methods. No interferences were seen when the performance of the FGC-MS method was challenged with ephedrine, pseudoephedrine, phenylpropanolamine, and phentermine. When compared to traditional GC-MS analysis, FGC-MS analysis provided a dramatic reduction in retention time for amphetamine (1.8 min vs. 4.12 min). For example, the FGC-MS method reduced overall run time for a batch of 56 specimens from 12.0 h to 7.25 h. This reduction in analysis time makes FGC-MS an attractive alternative to traditional GC-MS by allowing a laboratory greater flexibility in the purchase and use of capital equipment and in the assignment of laboratory personnel, all resulting in greater overall efficiency by decreasing reporting times for AMP, MAMP, and designer amphetamine positive specimens.

Gamma-hydroxybutyrate: bridging the clinical-analytical gap.

Laboratory detection of gamma-hydroxybutyrate (GHB) has been published as early as the 1960s. However, wide-scale use of GHB during the 1990s has led to the development of current analytic methods to test for GHB and related compounds. Detection of GHB and related compounds can be clinically useful in confirming the cause of coma in an overdose patient, determining its potential role in a postmortem victim, as well as evaluating its use in a drug-facilitated sexual assault victim. Analytical method sensitivity must be known in order to determine the usefulness and clinical application. Most laboratory cut-off levels are based on instrument sensitivity and will not establish endogenous versus exogenous GHB levels. Interpretation of GHB levels must include a knowledge base of endogenous GHB, metabolism of GHB and related compounds, as well as postmortem generation. Due to potential analytical limitations in various GHB methods, it is clinically relevant to specifically request for GHB as well as related GHB compounds if they are also in question. Various storage conditions (collection time, types of containers, use of preservatives, storage temperature) can also affect the analysis and interpretation of GHB and related compounds.

Cardiotoxicity associated with intentional ziprasidone and bupropion overdose.

BACKGROUND: Ziprasidone and bupropion are medications prescribed for mood and behavior disorders. They have apparently safe cardiac safety profiles in both therapeutic and supratherapeutic doses, but recently the Federal Drug Administration has issued a caution regarding ziprasidone use in combination with other drugs that are known to prolong the QTc interval. CASE REPORT: A 17-year-old male developed a widened QRS and a prolonged QTc interval following an overdose of ziprasidone and bupropion. He required hospital admission for aggressive cardiac monitoring and antidysrhythmic therapy, stabilizing to baseline by 80 hours postingestion. CONCLUSIONS: We present a case that underscores the potential cardiotoxicities of these medications. Ziprasidone and bupropion ingestion can be associated with cardiotoxicities that may require several days of aggressive cardiac monitoring and treatment.

Cardiotoxicity associated with intentional ziprasidone and bupropion overdose.

BACKGROUND: Ziprasidone (Geodon) and bupropion (Wellbutrin) are medications prescribed for mood and behavior disorders. They have apparently safe cardiac safety profiles in both therapeutic and supra-therapeutic doses. CASE REPORT: A 17-year-old male developed a widened QRS and a prolonged QTc interval following an overdose of ziprasidone and bupropion. He required hospital admission for aggressive cardiac monitoring and antidysrhythmic therapy, stabilizing to baseline by 80 hours post-ingestion. CONCLUSIONS: We present a case that underscores the potential cardiotoxicities of these medications. Ziprasidone and bupropion ingestion can be associated with cardiotoxicities that may require several days of aggressive cardiac monitoring and treatment.