title: Simultaneous LC-MS/MS determination of JWH-210, RCS-4, ∆(9)-tetrahydrocannabinol, and their main metabolites in pig and human serum, whole blood, and urine for comparing pharmacokinetic data.
abstract: A series of new synthetic cannabinoids (SC) has been consumed without any toxicological testing. For example, pharmacokinetic data have to be collected from forensic toxicological case work and/or animal studies. To develop a corresponding model for assessing such data, samples of controlled pig studies with two selected SC (JWH-210, RCS-4) and, as reference, ∆(9)-tetrahydrocannabinol (THC) should be analyzed as well as those of human cases. Therefore, a method for determination of JWH-210, RCS-4, THC, and their main metabolites in pig and human serum, whole blood, and urine samples is presented. Specimens were analyzed by liquid-chromatography tandem mass spectrometry and multiple-reaction monitoring with three transitions per compound. Full validation was carried out for the pig specimens and cross-validation for the human specimens concerning precision and bias. For the pig studies, the limits of detection were between 0.05 and 0.50 ng/mL in serum and whole blood and between 0.05 and 1.0 ng/mL in urine, the lower limits of quantification between 0.25 and 1.0 ng/mL in serum and 0.50 and 2.0 ng/mL in whole blood and urine, and the intra- and interday precision values lower than 15% and bias values within ±15%. The applicability was tested with samples taken from a pharmacokinetic pilot study with pigs following intravenous administration of a mixture of 200 μg/kg body mass dose each of JWH-210, RCS-4, and THC. The cross-validation data for human serum, whole blood, and urine showed that this approach should also be suitable for human specimens, e.g., of clinical or forensic cases.
authors.affiliation: Institute of Legal Medicine, Saarland University, Building 80.2, 66421, Homburg, Saar, Germany.
authors.forename: Nadine
authors.initials: N
authors.lastname: Schaefer
authors.forename: Mattias
authors.initials: M
authors.lastname: Kettner
authors.forename: Matthias W
authors.initials: MW
authors.lastname: Laschke
authors.forename: Julia
authors.initials: J
authors.lastname: Schlote
authors.forename: Benjamin
authors.initials: B
authors.lastname: Peters
authors.forename: Dietmar
authors.initials: D
authors.lastname: Bregel
authors.forename: Michael D
authors.initials: MD
authors.lastname: Menger
authors.forename: Hans H
authors.initials: HH
authors.lastname: Maurer
authors.forename: Andreas H
authors.initials: AH
authors.lastname: Ewald
authors.forename: Peter H
authors.initials: PH
authors.lastname: Schmidt
mesh_terms: D000818:Animals; D001774:Blood Chemical Analysis / Q000379:methods; D002186:Cannabinoids / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D006801:Humans; D013287:Illicit Drugs / Q000378:metabolism*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013045:Species Specificity; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D015813:Substance Abuse Detection / Q000379:methods*; D013552:Swine; D016482:Urinalysis / Q000379:methods
chemical_list: D002186:Cannabinoids; D013287:Illicit Drugs