Quantification of microdosed oral yohimbine and its major metabolite in human plasma in the picogram range.
Manuela VayMax SauterGerd MikusJuergen BurhennePublished in: Bioanalysis (2019)
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.
Keyphrases
- tandem mass spectrometry
- liquid chromatography
- solid phase extraction
- molecularly imprinted
- high throughput
- ultra high performance liquid chromatography
- high performance liquid chromatography
- mass spectrometry
- gold nanoparticles
- simultaneous determination
- high resolution
- quantum dots
- gas chromatography
- single cell
- clinical practice
- adverse drug
- amino acid