Manuela Vay1, Max Sauter1, Gerd Mikus1, Jürgen Burhenne1. 1. Department of Clinical Pharmacology & Pharmacoepidemiology, Im Neuenheimer Feld 410, Heidelberg University Hospital, Heidelberg 69120, Germany.
Abstract
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 & 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.
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 & 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.
Entities:
Keywords:
CYP2D6 phenotyping; microdosing; tandem mass spectrometry; ultra performance liquid chromatography; yohimbine
Authors: Margaux Fresnais; Esra Yildirim; Seda Karabulut; Dirk Jäger; Inka Zörnig; Julia Benzel; Kristian W Pajtler; Stefan M Pfister; Jürgen Burhenne; Walter E Haefeli; Rémi Longuespée Journal: Molecules Date: 2021-02-26 Impact factor: 4.411