Vay Manuela, Sauter Max, Mikus Gerd, Burhenne Jürgen
Department of Clinical Pharmacology & Pharmacoepidemiology, Im Neuenheimer Feld 410, Heidelberg University Hospital, Heidelberg 69120, Germany.
Bioanalysis. 2019 Aug;11(16):1459-1467. doi: 10.4155/bio-2019-0129. Epub 2019 Aug 14.
Pharmacokinetics after oral microdosing of the anticipated CYP2D6 substrate yohimbine and its metabolite 11-OH-yohimbine is potentially useful for drug-drug interaction trials and profiling of CYP2D6 enzyme activity. We developed an ultrasensitive ultra performance liquid chromatography coupled to tandem mass spectrometry assay for quantification of yohimbine and its main metabolite 11-OH-yohimbine in plasma with a linear calibration range of 5-2500 pg/ml and validated it according to US FDA's and EMA's guidelines. Sample preparation was performed using fast liquid-liquid extraction. The assay was applied for the determination of concentrations of yohimbine and 11-OH-yohimbine in plasma after oral administration of 50 μg yohimbine to two subjects. Ultrasensitive quantification of yohimbine and its metabolite enables the determination of their concentrations in plasma after microdosing which would be applicable to use in CYP2D6 phenotyping.
预期的细胞色素P450 2D6（CYP2D6）底物育亨宾及其代谢产物11-羟基育亨宾口服微剂量后的药代动力学，对于药物相互作用试验和CYP2D6酶活性分析可能具有重要意义。我们开发了一种超灵敏的超高效液相色谱-串联质谱分析法，用于定量血浆中的育亨宾及其主要代谢产物11-羟基育亨宾，线性校准范围为5-2500 pg/ml，并根据美国食品药品监督管理局（US FDA）和欧洲药品管理局（EMA）的指南对其进行了验证。采用快速液液萃取进行样品制备。该分析法用于测定两名受试者口服50μg育亨宾后血浆中育亨宾和11-羟基育亨宾的浓度。育亨宾及其代谢产物的超灵敏定量能够测定微剂量后它们在血浆中的浓度，这将适用于CYP2D6表型分析。
