Simultaneous measurement of epinastine and its metabolite, 9,13b-dehydroepinastine, in human plasma by a newly developed ultra-performance liquid chromatography-tandem mass spectrometry and its application to pharmacokinetic studies.
Epinastine is an antiallergic drug with high selectivity for histamine receptors. It has been reported that 9,13b-dehydroepinastine is present as a metabolite in vivo in humans, but there was little information about their pharmacokinetics (PKs) in humans. Although several analytical methods have been reported for epinastine analysis in different matrices, none are available for its metabolite. Therefore, the purpose of this study was to develop an analytical method to simultaneously measure epinastine and its metabolite, 9,13b-dehydroepinastine, in human plasma samples using an ultra-performance liquid chromatography-tandem mass spectrometer. Analytes were separated on a C18 column. Quantification of this analysis was performed on a triple-quadrupole mass spectrometer. Chromatograms showed high sensitivity, selectivity, and resolution with no interference with plasma constituents. Calibration curves for both epinastine and 9,13b-dehydroepinastine in human plasma were 0.1-50 ng/ml and displayed excellent linearity with correlation coefficients (r2 ) >0.99. The developed analytical method satisfied the criteria of international guidance and was validated. The method could be successfully applied to pharmacokinetic studies of epinastine and, for the first time, the metabolite kinetics of epinastine to 9,13b-dehydroepinastine in humans after oral administration of 20 mg epinastine hydrochloride tablets. Our study is expected to be useful in future studies such as dosage settings and clinical pharmacotherapy.
['Jeong|Seung-Hyun|SH|', 'Jang|Ji-Hun|JH|', 'Cho|Hea-Young|HY|', 'Lee|Yong-Bok|YB|https://orcid.org/0000-0002-0797-5324']
D000284:Administration, Oral D000328:Adult D002851:Chromatography, High Pressure Liquid D003984:Dibenzazepines D006801:Humans D007093:Imidazoles D016014:Linear Models D008297:Male D015203:Reproducibility of Results D012680:Sensitivity and Specificity D053719:Tandem Mass Spectrometry D055815:Young Adult
epinastine 9,13b-dehydroepinastine pharmacokinetics ultra-performance liquid chromatography-tandem mass spectrometer metabolite kinetics