Simultaneous Quantification of 13 Cannabinoids and Metabolites in Human Plasma by Liquid Chromatography Tandem Mass Spectrometry in Adult Epilepsy Patients

Simultaneous Quantification of 13 Cannabinoids and Metabolites in Human Plasma by Liquid Chromatography Tandem Mass Spectrometry in Adult Epilepsy Patients

A sensitive, robust method was developed and validated to quantitate 13 major natural cannabinoid parent and metabolite compounds in human plasma at or below 0.5 ng/mL. A liquid chromatography tandem mass spectrometry method was developed and validated to measure 13 cannabinoid compounds: cannabidio...

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Bibliographic Details
Published in:Therapeutic drug monitoring Vol. 41; no. 3; pp. 357 - 370
Main Authors: Roslawski, Michaela J, Remmel, Rory P, Karanam, Ashwin, Leppik, Ilo E, Marino, Susan E, Birnbaum, Angela K
Format: Journal Article
Language:English
Published: United States Lippincott Williams & Wilkins Ovid Technologies 01-06-2019
Subjects:
Adult
Cannabinoids - blood
Cannabinoids - metabolism
Cannabinoids - therapeutic use
Chemical compounds
Chromatography
Chromatography, Liquid - methods
Epilepsy - blood
Epilepsy - drug therapy
Epilepsy - metabolism
Humans
Limit of Detection
Mass spectrometry
Medical marijuana
Metabolites
Plasma
Plasma - chemistry
Sensitivity and Specificity
Tandem Mass Spectrometry - methods
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Summary:A sensitive, robust method was developed and validated to quantitate 13 major natural cannabinoid parent and metabolite compounds in human plasma at or below 0.5 ng/mL. A liquid chromatography tandem mass spectrometry method was developed and validated to measure 13 cannabinoid compounds: cannabidiol (CBD), cannabidiolic acid, cannabidivarin, cannabinol, cannabigerol, cannabigerolic acid, cannabichromene, Δ-tetrahydocannabinol (THC), Δ-tetrahydrocannabinolic acid A (THCA), Δ-tetrahydrocannabivarin (THCV), 11-hydroxy-Δ-tetrahydrocannbinol (11-OH-THC), 11-nor-9-carboxy-Δ-tetrahydrocannbinol (THC-COOH), and 11-nor-9-carboxy-Δ-tetrahydrocannabinol glucuronide (THC-COOH-glu). Samples (200 µL) were extracted through protein precipitation and separated with a Kinetex EVO C18 column and a 65%-95% gradient of methanol and 0.2% ammonium hydroxide/H2O at a flow rate of 0.4 mL/min. Samples were obtained from patients with epilepsy receiving cannabis for the treatment of seizures. The extracted lower limit of quantification was 0.05 ng/mL for CBD, cannabidivarin, cannabinol, and 11-OH-THC; 0.10 ng/mL for cannabidiolic acid, cannabigerol, cannabichromene, cannabigerolic acid, THC, THCA, and THCV; and 0.50 ng/mL for THC-COOH and THC-COOH-glu. Mean quality control intraday accuracy and precision for all analytes ranged 96.5%-104% and 2.7%-4.9%, respectively, whereas interday accuracy and precision ranged 98%-103.3% and 0.2%-3.6%, respectively. An absolute matrix effect was observed for some analytes, however, with minimal relative matrix effect. Lack of nonspecific drug binding to extraction glass and plasticware was verified. Patient CBD levels ranged from 0.135 to 11.13 ng/mL. The validated method met FDA guidelines for bioanalytical assays precision and accuracy criteria. The assay reliably confirmed the use of particular medical cannabis formulations in patient samples as well as reliably measured low CBD concentrations from single-dose CBD exposure.
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ISSN:0163-4356
1536-3694
DOI:10.1097/FTD.0000000000000583