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Aim: 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. Materials &amp; methods: 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. Conclusion: 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.

Quantification of Microdosed Oral Yohimbine and its Major Metabolite in Human Plasma in the Picogram Range