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An Atmospheric Pressure Chemical Ionization MS/MS Assay Using Online Extraction for the Analysis of 11 Cannabinoids and Metabolites in Human Plasma and Urine.


ABSTRACT: BACKGROUND:Although, especially in the United States, there has been a recent surge of legalized cannabis for either recreational or medicinal purposes, surprisingly little is known about clinical dose-response relationships, pharmacodynamic and toxicodynamic effects of cannabinoids such as ?9-tetrahydrocannabinol (THC). Even less is known about other active cannabinoids. METHODS:To address this knowledge gap, an online extraction, high-performance liquid chromatography coupled with tandem mass spectrometry method for simultaneous quantification of 11 cannabinoids and metabolites including THC, 11-hydroxy-?9-tetrahydrocannabinol, 11-nor-?9-tetrahydrocannabinol-9-carboxylic acid, 11-nor-?9-tetrahydrocannabinol-9-carboxylic acid glucuronide (THC-C-gluc), cannabinol, cannabidiol, cannabigerol, cannabidivarin, ?9-tetrahydrocannabivarin (THCV), and 11-nor-9-carboxy-?9-tetrahydrocannabivarin (THCV-COOH) was developed and validated in human urine and plasma. RESULTS:In contrast to atmospheric pressure chemical ionization, electrospray ionization was associated with extensive ion suppression in plasma and urine samples. Thus, the atmospheric pressure chemical ionization assay was validated showing a lower limit of quantification ranging from 0.39 to 3.91 ng/mL depending on study compound and matrix. The upper limit of quantification was 400 ng/mL except for THC-C-gluc with an upper limit of quantification of 2000 ng/mL. The linearity was r > 0.99 for all analyzed calibration curves. Acceptance criteria for intrabatch and interbatch accuracy (85%-115%) and imprecision (<15%) were met for all compounds. In plasma, the only exceptions were THCV (75.3%-121.2% interbatch accuracy) and cannabidivarin (interbatch imprecision, 15.7%-17.2%). In urine, THCV did not meet predefined acceptance criteria for intrabatch accuracy. CONCLUSIONS:This assay allows for monitoring not only THC and its major metabolites but also major cannabinoids that are of interest for marijuana research and clinical practice.

SUBMITTER: Klawitter J 

PROVIDER: S-EPMC5600652 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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An Atmospheric Pressure Chemical Ionization MS/MS Assay Using Online Extraction for the Analysis of 11 Cannabinoids and Metabolites in Human Plasma and Urine.

Klawitter Jelena J   Sempio Cristina C   Mörlein Sophie S   De Bloois Erik E   Klepacki Jacek J   Henthorn Thomas T   Leehey Maureen A MA   Hoffenberg Edward J EJ   Knupp Kelly K   Wang George S GS   Hopfer Christian C   Kinney Greg G   Bowler Russell R   Foreman Nicholas N   Galinkin Jeffrey J   Christians Uwe U   Klawitter Jost J  

Therapeutic drug monitoring 20171001 5


<h4>Background</h4>Although, especially in the United States, there has been a recent surge of legalized cannabis for either recreational or medicinal purposes, surprisingly little is known about clinical dose-response relationships, pharmacodynamic and toxicodynamic effects of cannabinoids such as Δ9-tetrahydrocannabinol (THC). Even less is known about other active cannabinoids.<h4>Methods</h4>To address this knowledge gap, an online extraction, high-performance liquid chromatography coupled wi  ...[more]

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