Confirmation of cannabinoid use by forensic toxicology testing in urine has been traditionally focused on ∆9-tetrahydrocannabinol (∆9-THC) with analysis of its major metabolite, 11-nor-9-carboxy-∆9-THC (∆9-cTHC), in free and conjugated forms. Legalization of hemp, however, has led to the widespread production and sale of cannabidiol (CBD) derivatives with psycho-activity, including ∆8-THC and ∆10-THC isomers. The increasing availability and growing use of isomer derivatives necessitate an expanded scope of cannabinoid confirmation test protocols. We report a quantitative, isomer-selective method of cannabinoid confirmation by liquid chromatography–tandem mass spectrometry determination of parent drug isomers (∆8-THC, ∆9-THC, ∆10-THC and CBD) as well as isomeric metabolites (∆8-cTHC and ∆9-cTHC). An efficient C18 phase chromatography on 1.6-µm solid core particles was used with a step gradient for near isocratic separation of both early-eluting THC metabolite isomers and later-eluting CBD and THC isomers. A rapid method of hydrolysis, dilution and analysis was employed for the quantitative co-determination of free and conjugated analytes, using stable isotope internal standardization. Method validation is reported, along with interference assessment from a prior confirmation method. Casework experience with the isomer-selective method revealed a 14% prevalence of ∆8-cTHC positive cases with a pattern of concomitant ∆8-THC and ∆9-THC use. A comparison of ∆8-cTHC and ∆9-cTHC phase two metabolism is also reported.

中文翻译：

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通过尿液中异构体选择性 UPLC-MS-MS 分析确认法医毒理学案例中的大麻素

通过尿液中的法医毒理学测试来确认大麻素的使用传统上集中于 Δ9-四氢大麻酚 (Δ9-THC)，并分析其主要代谢物 11-正-9-羧基-Δ9-THC (Δ9-cTHC) ，以游离和共轭形式。然而，大麻合法化导致了具有精神活性的大麻二酚 (CBD) 衍生物的广泛生产和销售，包括 Δ8-THC 和 Δ10-THC 异构体​​。异构体衍生物的可用性和使用量不断增加，需要扩大大麻素确认测试方案的范围。我们报告了一种通过液相色谱-串联质谱法测定母体药物异构体（Δ8-THC、Δ9-THC、Δ10-THC 和 CBD）以及异构代谢物（Δ8 -cTHC 和 Δ9-cTHC)。使用 1.6 µm 固体核心颗粒上的高效 C18 相色谱法和阶梯梯度，对早期洗脱的 THC 代谢物异构体和后期洗脱的 CBD 和 THC 异构体​​进行近等度分离。采用快速水解、稀释和分析方法，使用稳定同位素内标对游离和结合分析物进行定量共测定。报告方法验证以及先前确认方法的干扰评估。异构体选择性方法的案例工作经验显示，Δ8-cTHC 阳性病例的患病率为 14%，且伴有同时使用 Δ8-THC 和 Δ9-THC 的模式。还报告了 Δ8-cTHC 和 Δ9-cTHC 第二相代谢的比较。