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Clinical Chemistry

ISSN 0009-9147

16 papers in the library · 676 citations · publishing 1977-2025

Papers

Stereospecific Analysis and Enantiomeric Disposition of 3,4-Methylenedioxymethamphetamine (Ecstasy) in Humans

Clinical Chemistry July 1, 1999 John K. Fallon, Andrew T. Kicman, J. A. Henry et al. 137 citations

After a 40 mg oral dose of racemic MDMA (ecstasy) to eight men, the R-enantiomer reached higher and longer-lasting plasma levels than the S-enantiomer. The R-enantiomer's half-life was 5.8 hours versus 3.6 hours for S-MDMA, and its area under the curve was 2.4 times greater. More R-MDMA was excreted in urine (21.4% of dose) than S-MDMA (9.3%). The demethylated metabolite MDA appeared in smaller amounts, with S-MDA slightly exceeding R-MDA. Mathematical modeling of plasma enantiomer ratios over time suggests that analyzing stereochemical composition could help estimate time since drug intake for forensic purposes.

Usefulness of Saliva for Measurement of 3,4-Methylenedioxymethamphetamine and Its Metabolites: Correlation with Plasma Drug Concentrations and Effect of Salivary pH

Clinical Chemistry October 1, 2001 Mèonica Navarro, Simona Pichini, Magí Farré et al. 135 citations

After a single 100-mg dose of MDMA, concentrations in saliva ranged from 1728.9 to 6510.6 μg/L, peaking at 1.5 hours, then declining to a mean of 126.2 μg/L at 24 hours. The saliva-to-plasma ratio varied from 32.3 to 1.2, with a peak of 18.1 at 1.5 hours. Salivary pH decreased by 0.6 units after drug administration, from a predose mean of 7.4 to 6.9 at 1.5 hours and 6.8 at 4 hours. Measuring MDMA in saliva offers a noninvasive alternative to plasma testing for clinical and toxicologic studies.

Determination of the Designer Drugs 3,4-Methylenedioxymethamphetamine, 3,4-Methylenedioxyethylamphetamine, and 3,4-Methylenedioxyamphetamine with HPLC and Fluorescence Detection in Whole Blood, Serum, Vitreous Humor, and Urine

Clinical Chemistry December 1, 2000 Karine M. Clauwaert, Jan F. van Bocxlaer, Els A. de Letter et al. 68 citations

A method using high-performance liquid chromatography with fluorescence detection, confirmed by liquid chromatography-tandem mass spectrometry, accurately measures the designer drugs MDMA, MDEA, and their metabolite MDA in whole blood, serum, vitreous humor, and urine. The method is linear from 2 to 1000 μg/L for blood, serum, and vitreous humor, and from 0.1 to 5 mg/L for urine, with detection limits as low as 0.8 μg/L. Extraction recoveries exceed 70%, and imprecision ranges from 2.5% to 19%. In a rabbit thanatochemical distribution study, serum MDMA concentrations ranged from 5.3 to 685 μg/L, and whole blood MDMA from 19.7 to 710 μg/L. For routine toxicology urine samples, MDMA concentrations reached up to 157 mg/L.

Drug Testing in Blood: Validated Negative-Ion Chemical Ionization Gas Chromatographic–Mass Spectrometric Assay for Enantioselective Measurement of the Designer Drugs MDEA, MDMA, and MDA and Its Application to Samples from a Controlled Study with MDMA

Clinical Chemistry August 11, 2005 Frank T. Peters, Nele Samyn, C. T. J. Lamers et al. 49 citations

An assay was developed to measure the enantiomers of the designer drugs MDA, MDMA, and MDEA in small plasma volumes (0.2 mL or less). After extraction and derivatization, the enantiomers were separated by gas chromatography and detected by mass spectrometry within 17 minutes. The method was linear for MDA at 1–50 μg/L and for MDMA and MDEA at 5–250 μg/L per enantiomer, with extraction yields of 82.1%–95.3%. Applied to samples from a controlled study after a single 75 mg dose of racemic MDMA, the assay showed that R-(−)-MDMA concentrations significantly exceeded those of S-(+)-MDMA, with ratios always above 1.0 and increasing over time. S-(+)-MDA concentrations exceeded those of R-(−)-MDA, with ratios also increasing but remaining below 1.0.

Disposition of MDMA and Metabolites in Human Sweat Following Controlled MDMA Administration

Clinical Chemistry January 23, 2009 Allan J. Barnes, Bruno Spinosa de Martinis, David A. Gorelick et al. 38 citations

In a controlled study, 15 healthy volunteers with prior MDMA use received placebo, low (1.0 mg/kg), and high (1.6 mg/kg) oral doses of MDMA in random order while wearing sweat patches for up to 7 days. MDMA was the main substance found in 59.7% of patches, with concentrations up to 3007 ng/patch; its metabolite MDA appeared in 29.4% of patches at lower levels, while other metabolites were undetected. At the 25-ng/patch threshold, 35% of patches were positive for MDMA. Sweat testing reliably detects MDMA use, but high variability in excretion means results should be interpreted qualitatively, not quantitatively.

Radioimmunoassay of lysergic acid diethylamide (LSD) in serum and urine by using antisera of different specificities.

Clinical Chemistry February 1, 1977 W A Ratcliffe, S.m. Fletcher, A.c. Moffat et al. 38 citations

High-titre antisera were raised to two LSD-bovine serum albumin conjugates, each specific for different parts of the LSD molecule. These antisera enabled a double-antibody radioimmunoassay with a detection limit of about 0.4 micrograms of LSD per liter of unextracted urine or serum, with no nonspecific interference from urine, serum, or common drugs. Immunoassay values from the two antisera correlated well (r = 0.91), though the antiserum linked via the indole nitrogen gave consistently higher results for samples from people who had taken LSD due to greater cross-reactivity with LSD metabolites. Using two such antisera provides a more specific screening procedure for LSD abuse and allows measurement of metabolites for which no satisfactory method previously existed.

Short-Term Stability of Lysergic Acid Diethylamide (LSD), N-Desmethyl-LSD, and 2-Oxo-3-hydroxy-LSD in Urine, Assessed by Liquid Chromatography–Tandem Mass Spectrometry

Clinical Chemistry September 1, 2002 Gisela Skopp, Lucia Pötsch, Rainer Mattern et al. 37 citations

Lysergic acid diethylamide (LSD) is a potent hallucinogen that is rapidly metabolized and unstable in biological fluids, making its detection in urine challenging. After a typical street dose of 40–120 μg, LSD concentration in urine falls below 1 μg/L within hours. Metabolites N-desmethyl-LSD (nor-LSD) and 2-oxo-3-hydroxy-LSD (O-H-LSD) have been identified, with O-H-LSD measured at concentrations severalfold higher (0.02–21.4 μg/L). Liquid chromatography–tandem mass spectrometry (LC-MS/MS) improves detection. LSD decomposes in urine exposed to heat, sunlight, or ultraviolet light, but stability data on its major metabolites were lacking. This study assessed the stability of LSD, O-H-LSD, and nor-LSD in urine under different storage conditions using LC-MS/MS, aiming to inform sample transport and storage practices.

Two-Dimensional Gas Chromatography/Electron-Impact Mass Spectrometry with Cryofocusing for Simultaneous Quantification of MDMA, MDA, HMMA, HMA, and MDEA in Human Plasma

Clinical Chemistry December 19, 2007 Erin A Kolbrich, Ross H. Lowe, Marilyn A. Huestis 36 citations

A two-dimensional gas chromatography–mass spectrometry method with cryofocusing simultaneously quantifies MDMA, its metabolites MDA, HMMA, and HMA, and MDEA in human plasma. Limits of quantification were 1.0 μg/L for MDA and 2.5 μg/L for the other four compounds. Calibration curves were linear up to 100 μg/L for MDA and HMA and up to 400 μg/L for MDEA, MDMA, and HMMA, with correlation coefficients above 0.997. Extraction efficiencies from plasma were at least 85%, recoveries ranged from 85.6% to 107.2% of target, and intra- and interassay imprecision was below 8.5% at three concentrations. None of 66 tested exogenous compounds interfered. The assay achieves low quantification limits suitable for pharmacokinetic studies and may apply to other analytes and complex matrices.

Negative-Ion Chemical Ionization Gas Chromatography–Mass Spectrometry Assay for Enantioselective Measurement of Amphetamines in Oral Fluid: Application to a Controlled Study with MDMA and Driving Under the Influence Cases

Clinical Chemistry March 2, 2007 Frank T. Peters, Nele Samyn, Thomas Kræmer et al. 36 citations

A gas chromatography–mass spectrometry method using negative-ion chemical ionization was developed to separately measure the left- and right-handed forms (enantiomers) of amphetamine, methamphetamine, MDA, MDMA, and MDEA in oral fluid. After adding a buffer and a derivatizing agent, the enantiomers were extracted and analyzed. The method was linear from 5–250 μg/L per enantiomer for MDA and from 25–1250 μg/L per enantiomer for the other drugs. Recoveries and precision were acceptable except for MDEA. When applied to samples from a controlled MDMA study and real driving-under-the-influence cases, the oral fluid concentrations and enantiomer ratios did not reliably predict plasma levels.

Urinary Excretion Kinetics of 3,4-Methylenedioxymethamphetamine (MDMA, Ecstasy) and Its Phase I and Phase II Metabolites in Humans following Controlled MDMA Administration

Clinical Chemistry October 7, 2011 Andrea E. Schwaninger, Markus R. Meyer, Allan J. Barnes et al. 33 citations

After oral MDMA (ecstasy) intake, human urine contains mostly sulfate and glucuronide conjugates of MDMA metabolites, with sulfates present at higher concentrations than glucuronides. More than 90% of the metabolites DHMA and HMMA were excreted as conjugates. HMMA sulfate had the longest detection window in urine. The ratio of HMMA sulfate to glucuronide was 2.0, and the ratio of DHMA 3-sulfate to 4-sulfate was 5.3 during the first 24 hours, matching predictions from earlier lab experiments. These findings can improve direct urine analysis for MDMA and its metabolites in clinical and forensic toxicology.

Sensitive Gas Chromatography-Mass Spectrometry Method for Simultaneous Measurement of MDEA, MDMA, and Metabolites HMA, MDA, and HMMA in Human Urine

Clinical Chemistry July 20, 2006 Stéphane Pirnay, T. T. Abraham, Marilyn A. Huestis 29 citations

A sensitive gas chromatography-mass spectrometry method was developed and validated to simultaneously measure MDEA, MDMA, and its metabolites (HMA, MDA, HMMA) in human urine. The method involves acid hydrolysis of 1 mL urine, solid-phase extraction, and derivatization before analysis. Limits of quantification were 25 μg/L for all analytes, with linear calibration up to 5000 μg/L. Extraction efficiencies exceeded 85.5%, and imprecision (coefficient of variation) was below 15% at tested concentrations. The assay meets federal workplace drug testing guidelines for these substances.

Interference with testing for lysergic acid diethylamide

Clinical Chemistry April 1, 1997 Detlef Ritter, Cherise M Cortese, Linda C Edwards et al. 24 citations

A high rate of false-positive LSD results (4.2%) occurred in urine samples from psychiatric patients when using the Emit assay. These positive results could not be confirmed by two different radioimmunoassays or by gas chromatography–mass spectrometry. Adding therapeutic medications commonly prescribed to these patients to normal urine samples produced positive LSD results with the Emit assay, indicating that those drugs interfere specifically with the Emit test for LSD.

MDMA and MDA cross reactivity observed with Abbott TDx amphetamine/methamphetamine reagents.

Clinical Chemistry May 1, 1988 José Manuel Ramos, R.l. Fitzgerald, Alphonse Poklis 10 citations

The Abbott TDx amphetamine/methamphetamine reagents show cross-reactivity with MDMA and MDA, meaning these drugs can produce false-positive results when testing for amphetamines. This finding has implications for forensic toxicology and clinical drug testing, as it may lead to misidentification of substances.

Indirect enzyme-linked immunosorbent assay for the quantitative estimation of lysergic acid diethylamide in urine

Clinical Chemistry May 1, 1998 Sarah Kerrigan, Donald E Brooks 6 citations

A new antibody targeting LSD enabled the development of an indirect ELISA that measures LSD in urine with better performance than a commercial assay. The test uses 50 μL of urine and detects concentrations from ng/L to μg/L. The limit of detection is 8 ng/L, compared to 85 ng/L for the commercial assay, and analytical recoveries range from 98–106%. At 0.1 μg/L, the intraassay coefficient of variation (CV) was 2.4% (n=8), versus 6.0% at 0.5 μg/L for the commercial assay (n=20). The upper and lower quantification limits are 7 μg/L and 50 ng/L. Cross-reactivity with 24 related substances was evaluated. The new assay offers improved sensitivity and precision, enabling more certain quantitative estimation of LSD in urine at lower concentrations.

B-305 High Specificity Homogeneous Enzyme Immunoassay for Ketamine

Clinical Chemistry October 1, 2025 Se Yeon Oh, Kim Pham, Rajendra Singh et al.

A new immunoassay, the ARK Ketamine II Assay, accurately detects ketamine in human urine at two cutoff concentrations (50 and 100 ng/mL) with high precision and specificity. In tests on 223 negative urine samples, the assay correctly identified all as negative, including 22 that had produced a response above the detection limit in the earlier version. For positive samples confirmed by LC-MS/MS, the assay showed 100% sensitivity and 100% specificity at both cutoffs. The assay also cross-reacts with the major metabolite nor-ketamine at about 45–47%, while cross-reactivity to methoxetamine is less than 0.3%. The method is suitable for routine clinical chemistry analyzers.

B-302 Psychedelics and Dissociative Anesthetics: Concentrations in Suspected Impaired Driving Investigations, 2024

Clinical Chemistry October 1, 2025 Stephanie Marco

In 2024, among 328 suspected driving-under-the-influence cases, the most common psychedelic or dissociative drug detected was phencyclidine (PCP, 220 cases), followed by MDMA (81 cases) and ketamine (22 cases). LSD and psilocin were found in only 2 and 5 cases, respectively. Drug concentrations varied widely, with ketamine ranging from 25 to 880 ng/mL, LSD from 3 to 9.8 ng/mL, PCP from 6 to 270 ng/mL, and MDMA from 5.5 to 850 ng/mL. Most drivers also had other central nervous system depressants in their blood. The findings highlight safety concerns for driving as psychedelic therapies become more available.