xlr-11 and n-pentanoic-acid

`Herbal mixtures` containing synthetic cannabinoid receptor agonists (SCRAs) are promoted as legal alternative to marihuana and are easily available via the Internet. Keeping analytical methods for the detection of these SCRAs up-to-date is a continuous challenge for clinicians and toxicologists due to the high diversity of the chemical structures and the frequent emergence of new compounds. Since many SCRAs are extensively metabolized, analytical methods used for urine testing require previous identification of the major metabolites of each compound.. The aim of this study was to identify the in vivo major metabolites of nine SCRAs (AM- 694, AM-2201, JWH-007, JWH-019, JWH-203, JWH-307, MAM-2201, UR-144, XLR-11) for unambiguous detection of a drug uptake by analysis of urine samples.. Positive urine samples from patients of hospitals, detoxification and therapy centers as well as forensic-psychiatric clinics were analyzed by means of liquid chromatography-tandem mass spectrometry (LC-MS/MS) and liquid chromatography-quadrupole time-of-flight mass spectrometry (LCqToF- MS) for investigation of the major in vivo metabolites.. For all investigated SCRAs, monohydroxylation, dihydroxylation and/or formation of the Nhexanoic/ pentanoic acid metabolites were among the most abundant metabolites detected in human urine samples. Substitution of the fluorine atom was observed to be an important metabolic reaction for compounds carrying an N-(5-fluoropentyl) side chain. N-Dealkylated metabolites were not detected in vivo.. The investigated metabolites facilitate the reliable detection of drug uptake by analysis of urine samples. For distinction between uptake of the fluorinated and the non-fluorinated analogs, the N-(4-hydroxypentyl) metabolite of the non-fluorinated analog was identified as a useful analytical target and consumption marker.

Topics: Cannabinoid Receptor Agonists; Cannabinoids; Chromatography, Liquid; Humans; Indoles; Naphthalenes; Pentanoic Acids; Substance Abuse Detection; Tandem Mass Spectrometry

Analysis of drugs in hair is often used as a routine method to obtain detailed information about drug ingestion. However, few studies have been conducted on disposition of synthetic cannabinoids including cyclopropylindoles (UR-144 and XLR-11) and their metabolites in hair. XLR-11 has been widely abused in South Korea recently. Identification of metabolites in hair can be an important proof of synthetic cannabinoids use because it can exclude the possibility of passive smoke exposure. In this study, we described a quantitative analytical method of XLR-11 and its metabolites (UR-144, UR-144 N-5-hydroxypentyl metabolite, UR-144 N-4-hydroxypentyl metabolite, UR-144 N-pentanoic acid metabolite and XLR-11 N-4-hydroxypentyl metabolite) in hair by liquid chromatography with ESI-MS/MS. The target analytes were extracted with methanol from washed and cut hair samples and the extracts were evaporated, filtered and analyzed by LC-MS/MS with electrospray ion source in positive-ionization mode. JWH-018-d9 and JWH-018 N-5-hydroxypentyl metabolite-d5 were used as internal standards. Chromatographic separation was completed within 15 min. No interferences were detected in 10 blank hair samples. In intra- and inter-assay precision and accuracy study, CV (%) and bias (%) were below 12. The limit of detection (LOD) was 0.1∼2 pg/mg and the limit of quantification (LOQ) was 0.2-2 pg/mg, respectively. The validation results proved that the method was selective, accurate and precise with acceptable linearity within calibration range. No significant variation was observed by different sources of matrices. This method was applied to hair samples from 14 individual suspects of XLR-11 use. In this result, XLR-11, UR-144, UR-144 N-5-hydroxypentyl metabolite and UR-144 N-pentanoic acid metabolite, XLR-11 N-4-hydroxypentyl metabolite were detected. The concentration of XLR-11 as a parent drug was much higher than other metabolites. UR-144 N-5-hydroxy metabolite and UR-144 N-pentanoic acid were detected mainly in the authentic hair samples from suspected of XLR-11 use. UR-144 N-4- hydroxypentyl metabolite was not detected in all cases.

Topics: Calibration; Cannabinoids; Chromatography, Liquid; Hair; Humans; Indoles; Limit of Detection; Methanol; Pentanoic Acids; Reproducibility of Results; Spectrometry, Mass, Electrospray Ionization; Substance Abuse Detection; Substance-Related Disorders; Tandem Mass Spectrometry