Biomedical subjects

Aaron Jacobs

Publications and source records attributed to Aaron Jacobs.

6 recordsLinked to original sources

PubMed2006

Distribution of ether in two postmortem cases.

Diethyl ether (ether) is a volatile liquid that was used in the 1800s as an anesthetic agent; however, it is no longer used for this purpose, partly because of its odor and flammability. Two postmortem cases in which ether was detected are presented. The first case was an 18-year-old male found hanging from a basement ceiling brace in a semi-sitting position with a gas mask covering his face. A container of Prestone starting fluid and a bong were found on the floor close to the body. The second case was a 20-year-old male found unresponsive in his dormitory room with two black plastic trash bags secured over his head. Two saturated rags and a resealable bag containing a clear liquid were contained within these trash bags. An almost empty can of Tradco starting fluid was also found at the scene. Ether concentrations were determined by headspace gas chromatography-mass spectrometry in the selective ion monitoring mode. In case #1, the medical examiner ruled that the cause of death was asphyxia due to hanging; the manner of death was undetermined. In case #2, the medical examiner ruled that the cause of death was asphyxia and the manner of death was suicide.

Adolescent↗

PubMed2005

Quantitative and isomeric determination of amphetamine and methamphetamine from urine using a nonprotic elution solvent and R(-)-alpha-methoxy-alpha-trifluoromethylphenylacetic acid chloride derivatization.

Forensic Urine Drug Testing Laboratories often requires two confirmatory methods for a methamphetamine positive screen. First, methamphetamine is identified and quantitated using gas chromatography-mass spectrometry. If the total methamphetamine concentration is above the administrative cutoff level, the isomeric composition must be determined. This eliminates a possible contribution by over-the-counter cold medications that contain l-methamphetamine (Vick's inhalers). Products that contain only the l-isomer of methamphetamine must be distinguishable from prescription or illicitly manufactured methamphetamine, which consists mainly of the d-isomer. Optically impure derivatizing reagents will produce an impure mixture from a pure isomeric compound. Therefore, methods utilizing impure reagents can prove problematic when interpreting results. Use of an optically pure chiral derivatizing reagent, such as R(-)-alpha-methoxy-alpha-trifluoromethylphenylacetic acid chloride, allows for the creation and measurement of chromatographically separable isomeric compounds. The novel method described here utilizes a polymer-based solid-phase column adapted to a positive pressure manifold extraction system and a one-step derivatization process that occurs directly in the elution solvent. This methodology eliminates an elution solvent dry-down step that may adversely affect recovery of volatile amphetamine compounds. Although the method was designed for the quantitative analysis of the isomers of amphetamine and methamphetamine, it can be adapted for use with a wide range of phenethylamines including methylenedioxyamphetamine, N-methylenedioxymethamphetamine, and possibly N-methylenedioxyethylamphetamine. The linear range for quantitation was 25-10,000 ng/mL for d,l-methamphetamine and d,l-amphetamine, and correlation coefficients were 0.997 or better. The coefficient of variation for all four analytes did not exceed 2.8%. Concentrations analyzed ranged from 500 to 4000 ng/mL (n=40). The method allows for a simple and accurate quantitation and isomeric determination of amphetamine and methamphetamine using a process that eliminates extraction and derivatization complications common in current methods.

Amphetamine↗

PubMed2005

Spectrophotometric detection of iodide and chromic (III) in urine after oxidation to iodine and chromate (VI).

Tests for oxidizing adulterants in urine are a continuing challenge to the drug-testing program. Iodine was found to destroy morphine and 6-acetylmorphine almost immediately. The effects were less evident on 11 -nor-delta9-tetrahydrocannabinol-9-carboxylic acid (THC-acid). When the urine solution was tested for iodine by a chromogenic substrate, 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS), no iodine was detected. Masking drug and adulterant simultaneously made iodine a preferred oxidizing adulterant for drug abusers. In this study, the reduced iodide was oxidized by sodium nitrite to iodine. The excess nitrite was decomposed by sulfamic acid and the iodine was detected by ABTS. Linearity was 12.7 to 635 mg/L (0.1 to 5 mmol/L, y = 0.9966x + 0.0016, R2 = 1.0000). Precisions (coefficient of variation) were within +/- 4.1% and quantitative accuracies were within 97% of expected values (n=5). Chromate, iodate, periodate, and persulfate interfered with the method. To alleviate the problem, the positive specimens were tested again by an iodine-specific method. After oxidation, the samples were treated with sodium azide and ammonium thiocyanate. In presence of thiocyanate, the azide reduced iodine to iodide almost immediately, and the solutions showed negative response to ABTS. The results were compared with that of a control group tested without thiocyanate. When iodine was present, the ratios of thiocyanate to control were less than 6%. Chromate was also found to destroy THC-acid in urine, and during storage most of the chromate changed to chromic (III). In this study, chromic was oxidized to chromate by hydrogen peroxide and sodium hydroxide and detected by 1,5-diphenylcarbazide. Linearity was 5.2 to 156 mg/L (0.1 to 3.0 mmol/L, y = 1.0285x - 0.0034, R2 = 0.9998). Precisions were within +/- 8.5% and quantitative accuracies were within 92% of expected values (n=5). The test was not interfered by other oxidizing agents. Both iodide and chromic oxidation methods showed urine backgrounds less than 1.27 and 0.52 mg/L, respectively (< 0.01 mmol/L). It indicated that a response more than 10 times of the background could be considered as oxidant contamination or adulteration of urine specimens.

Chromium↗

PubMed2004

Enantiomeric separation and quantitation of (+/-)-amphetamine, (+/-)-methamphetamine, (+/-)-MDA, (+/-)-MDMA, and (+/-)-MDEA in urine specimens by GC-EI-MS after derivatization with (R)-(-)- or (S)-(+)-alpha-methoxy-alpha-(trifluoromethy)phenylacetyl chloride (MTPA).

In drug testing, the presence of methamphetamine in urine is generally confirmed by a gas chromatography-mass spectrometry (GC-MS) method. Derivatization of the compound to a perfluoroalkylamide, prior to confirmation, typically yields better chromatographic separation. Once methamphetamine is detected, a second GC-MS test is necessary to distinguish positive results from the use of over-the-counter medication, Vicks inhaler, or from use of a prescription drug, selegiline (Deprenyl). R-(-)-Methamphetamine is the urinary product from legitimate use of these medications. The second GC-MS test is to confirm illicit use of (S)-(+)-methamphetamine. In the procedure, the two methamphetamine isomers are changed to the chromatographically separable diastereomers by a chiral derivatizing agent, (S)-(-)-trifluoroacetylprolyl chloride (TPC). But the method has inherent limitations. Racemization of the reagent produces mixed diastereomers even from pure (S)-(+)-methamphetamine. Instead of using TPC, we utilized (R)-(-)-alpha-methoxy-alpha-(trifluoromethyl)phenylacetyl chloride (MTPA) to prepare the amides of diastereomers of methamphetamine. No racemization was observed with this reagent. The method was extended to resolve GC peaks of (R)-(-)- and (S)-(+)-isomers of amphetamine, 3,4-methylenedioxyamphetamine (MDA), N-methyl-MDA (MDMA), and N-ethyl-MDA (MDEA). Three ions from the drug and two ions from the deuterated internal standard were monitored to characterize and quantitate the drugs. For MDEA, only one ion was used. The quantitation was linear over 25 to 5000 ng/mL for MDEA and 25 to 10,000 ng/mL for all other drugs. Correlation coefficients were > 0.996. Precision calculated as the coefficient of variation at the calibrator concentration of 500 ng/mL was within +/- 11% for all drugs. The method was applied to test 43 urine specimens. In 91% of the methamphetamine-positive specimens, only the (S)-(+)-isomer was detected. In all MDMA-positive specimens, the concentrations of (R)-(-)-isomer were greater than the (S)-(+)-isomer indicating longer retention of (R)-(-)-isomer in the human body. The specimen concentrations (R + S) compared well with that of a non-chiral method that used 4-carboethoxyhexafluorobutyryl chloride as derivatizing agent. But the MTPA method has some advantage. It alone can replace the two GC-MS methods needed to confirm the presence of (S)-(+)-isomers of amphetamine and methamphetamine.

3,4-Methylenedioxyamphetamine↗

PubMed2004

Comparison of the Microgenics CEDIA heroin metabolite (6-AM) and the Roche Abuscreen ONLINE opiate immunoassays for the detection of heroin use in forensic urine samples.

Current Department of Defense (DoD) and Department of Health and Human Services (HHS) procedures for the detection of heroin abuse by testing urine utilize an initial opiate (codeine/morphine) immunoassay (IA) screen followed by gas chromatography-mass spectrometry (GC-MS) confirmation of 6-acetylmorphine (6-AM), if the morphine concentration is above established cutoff. An alternative to the current opiates screen for heroin abuse is the direct IA for the metabolite of heroin, 6-acetylmorphine. In this regard, the performance of the Microgenics CEDIA heroin metabolite (6-AM) screening reagent was assessed. This evaluation was conducted on the P module of a Hitachi Modular automated IA analyzer calibrated using 6-AM at 10 ng/mL. Reproducibility, linearity, accuracy, sensitivity, and interferences associated with use of the 6-AM IA reagent were evaluated. The IA reagent precision (percent coefficient of variation (%CV)) around each of seven standards was less than 0.63%, with a linearity (r(2)) value of 0.9951. A total of 37,713 active duty service members' urine samples were analyzed simultaneously using the CEDIA heroin metabolite (6-AM) reagent and the Roche Abuscreen ONLINE opiate reagent to evaluate both the prevalence rate of 6-AM in the demographic group and the sensitivity and specificity of the reagents for the detection of heroin use. Of the 37,713 samples tested using the CEDIA heroin metabolite (6-AM) reagent, three samples screened positive at the DoD and HHS cutoff of 10 ng/mL. One of the three samples confirmed positive for 6-AM by GC-MS above the cutoff of 10 ng/mL, the two remaining samples confirmed negative for 6-AM at a GC-MS limit of detection (LOD) of 2.1 ng/mL. In contrast, the Roche Abuscreen ONLINE opiate IA produced 74 opiate-positive results for codeine/morphine, with 6 of the 74 specimens confirming positive for morphine above the DoD cutoff concentration of 4000 ng/mL (8% DoD morphine confirmation rate), only one of the 74 opiate-positive screen specimens confirmed positive for 6-AM above the 10 ng/mL GC-MS cutoff concentration. As a further check of the sensitivity and specificity of the Microgenics 6-AM IA reagent, human urine samples (n = 87) known to contain 6-AM by GC-MS, were re-analyzed using both IA reagents. All 87 of the samples screened positive using the CEDIA heroin metabolite (6-AM) assay. However, using the Roche ONLINE opiate reagent, 12 of the known 6-AM positives screened negative at the DoD and HHS screening cutoff of 2000 ng/mL (morphine). Of the remaining 75 samples that screened positive by the ONLINE opiate reagent, five of the samples did not contain morphine above the DoD GC-MS cutoff concentration of 4000 ng/mL and would not have required 6-AM analysis. However, under the HHS GC-MS morphine cutoff concentration of 2000 ng/mL all 75 samples would have required 6-AM analysis. Furthermore, using the current DoD opiate screen, 17 out of 87 samples known to contain 6-AM would have gone undetected (19.5% false-negative rate); additionally, even under the more stringent HHS opiate screening standards 12 out of the 87 samples known to contain 6-AM would also have gone undetected (13.8% false-negative rate). The Microgenics CEDIA heroin metabolite (6-AM) reagent assay appears well adapted for the rapid and specific detection of heroin abuse as an alternative for, or an adjunct test to, the current opiates (codeine/morphine) IA screening procedure.

Calibration↗

PubMed2002

Effects of oxidizing adulterants on detection of 11-nor-delta9-THC-9-carboxylic acid in urine.

Bleach, nitrite, chromate, and hydrogen peroxide-peroxidase are effective urine adulterants used by the illicit drug users to conceal marijuana-positive results. Methods for detecting nitrite and chromate are available. Effects of other oxidizing agents that could possibly be used as adulterants and are difficult to detect or measure are presented in this report. Urine samples containing 40 ng/mL of 11-nor-delta9-THC-9-carboxylic acid (THC-acid) were treated with 10 mmol/L of commonly available oxidizing agents. Effects of horseradish peroxidase of activity 10 unit/mL and extracts from 2.5 g of red radish (Raphanus sativus, Radicula group), horseradish (Armoracia rusticana), Japanese radish (Raphanus sativus, Daikon group), and black mustard seeds (Brassica nigra), all with 10 mmol/L of hydrogen peroxide, were also examined. After 5 min, 16 h and 48 h of exposure at room temperature (23 degrees C) the specimens were tested by a gas chromatographic-mass spectrometric method for THC-acid. A control group treated with sodium hydrosulfite to reduce the oxidants, was also tested to investigate the effect of oxidizing agents on THC-acid in the extraction method. THC-acid was lost completely in the extraction method when treated with chromate, nitrite, oxone, and hydrogen peroxide/ferrous ammonium sulfate (Fenton's reagent). Some losses were also observed with persulfate and periodate (up to 25%). These oxidants, and other oxidizing agents like permanganate, periodate, peroxidase, and extracts from red radish, horseradish, Japanese radish and black mustard seeds destroyed most of the THC-acid (> 94%) within 48 h of exposure. Chlorate, perchlorate, iodate, and oxychloride under these conditions showed little or no effect. Complete loss was observed when THC-acid was exposed to 50 mmol/L of oxychloride for 48 h. Several oxidizing adulterants that are difficult to test by the present urine adulterant testing methods showed considerable effects on the destruction of THC-acid. The time and temperature for these effects were similar to those used by most laboratories to collect and test specimens. In several cases, the loss of THC-acid was > 94%.

Armoracia↗