Simultaneous quantification of 37 synthetic cannabinoid metabolites in human urine by liquid chromatography-tandem mass spectrometry

Abstract

Despite efforts by legal authorities to control the abuse of synthetic cannabinoids, new derivatives have continually emerged on the market to circumvent regulations, and its abuse has become a threat to public health. Thus, development of analytical methods for confirming drug intake in biological fluids is essential to ensure effective drug control and to address further drug intoxication cases. Herein, a sensitive and reliable liquid chromatography-tandem mass spectrometry method was established and validated for the simultaneous determination of 37 synthetic cannabinoid metabolites, such as N-hydroxypentyl and carboxy metabolites, using 100 ll of urine. Urine specimens were treated by enzymatic hydrolysis and solid-phase extraction. Limits of detection for the evaluated drugs ranged from 0.1 to 1 ng/ml, and the linear range spanned from 0.25 or 1 to 100 ng/ml. Precision and accuracy bias were 1.4-12.1 % and -7.2-7.2 %, respectively. Matrix effects biases were in the range of 0.4 to 10.1 %, and extraction recoveries were 65-99 %. In addition, all analytes were stable under storage conditions of 4°C and -20°C for 14 days, and after three freeze-thaw cycles. The developed method was successfully applied to actual urine specimens obtained from synthetic cannabinoid users. The present method enabled simultaneous quantification of 37 synthetic cannabinoid metabolites, including their regioisomers, in urine in the field of clinical and forensic toxicology.

Identification and quantification of predominant metabolites of synthetic cannabinoid MAB‐CHMINACA in an authentic human urine specimen

“…Concentrations of M1 and M11 in each sample were determined after 7, 14, 21, and 28 days by LC–MS/MS. Metabolites M1 and M11 in urine specimens were found to be relatively stable under all conditions examined (ranged from 70.9 to 124%), as was also reported in another article showing excellent stabilities of synthetic cannabinoid metabolites in human urine …”

Identification and quantification of metabolites of AB-CHMINACA in a urine specimen of an abuser

“…In our previous study [16], it was impossible to detect unchanged AB-CHMINACA from the urine specimen of the same individual. Very recently, Jang et al [17] reported the levels of metabolites of synthetic cannabinoids having aliphatic side chain structures (pentyl, butyl and hexyl aliphatic chains) in authentic urine specimens; their levels ranged from 0.3 to 420 ng/ml. However, the level of 420 ng/ml was exceptional; all levels (20 level data) except the highest one were not greater than 38 ng/ml.…”

“…As reported by our group [15,16], the unchanged synthetic cannabinoids could be detected from solid tissues, but not from urine specimens. To disclose the abuse of synthetic cannabinoid(s) using urine specimens, it is essential to identify and quantify the predominant metabolite(s) in human urine [17]. As to AB-CHMINACA, only one report [18] has appeared; they studied in vitro metabolism of AB-CHMINACA using human liver microsomes, followed by the estimation of metabolites by liquid chromatography-time-of-flig ht-mass spectrometry.…”

Screening, quantification, and confirmation of synthetic cannabinoid metabolites in urine by UHPLC–QTOF–MS

“…However, these methods can only identify the compounds they are designed for, and updates are not easily performed. A number of quantitative screening methods in urine by LC–MS/MS have previously been published . High resolution mass spectrometry (HRMS) with quadrupole time of flight (QTOF) instrumentation that acquires full spectrum data is not limited by scan/dwell times, and introducing new masses/formulas to the method will not affect the detection of the previously included ones.…”