TY - JOUR T1 - Simultaneous quantification of vortioxetine, carvedilol and its active metabolite 4-hydroxyphenyl carvedilol in rat plasma by UPLC-MS/MS: Application to their pharmacokinetic interaction study. AU - Huang,Yi, AU - Zheng,Shuangli, AU - Pan,Yongyang, AU - Li,Tao, AU - Xu,Zhi-Sheng, AU - Shao,Meng-Meng, Y1 - 2016/05/19/ PY - 2016/02/20/received PY - 2016/05/17/revised PY - 2016/05/18/accepted PY - 2016/6/6/entrez PY - 2016/6/6/pubmed PY - 2017/5/10/medline KW - 4-hydroxyphenyl carvedilol KW - Carvedilol KW - Pharmacokinetics KW - UPLC–MS/MS KW - Vortioxetine SP - 184 EP - 190 JF - Journal of pharmaceutical and biomedical analysis JO - J Pharm Biomed Anal VL - 128 N2 - To establish a rapid and sensitive ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method for the determination of vortioxetine, carvedilol and its metabolite 4-hydroxyphenyl carvedilol in rat plasma. The analytes and the internal standard (diazepam) were separated on an Acquity UPLC BEH C18 chromatography column (2.1mm×50mm, 1.7μm) using gradient elution with a mobile phase of acetonitrile and 0.1% formic acid in water at a flow rate of 0.4mL/min. The detection was performed on a triple quadrupole tandem mass spectrometer by multiple reaction monitoring (MRM) mode to monitor the precursor-to-product ion transitions of m/z 299.2→150.1 for vortioxetine, m/z 407.2→100.3 for carvedilol, m/z 423.2→100.1 for 4-hydroxyphenyl carvedilol and m/z 285.2→193.1 for diazepam (IS) using a positive electrospray ionization interface. The method was validated over a concentration range of 0.5-100ng/mL for vortioxetine, 0.5-1000ng/mL for carvedilol and 0.1-50ng/mL for 4-hydroxyphenyl carvedilol. Total time for each chromatograph was 3.0min. The intra- and inter-day precision and accuracy of the quality control samples at low, medium, and high concentration levels exhibited relative standard deviations (RSD)<11.6% and the accuracy values ranged from -12.2% to 11.3%. The analytical method was successfully applied to a pharmacokinetic interaction study of vortioxetine and carvedilol after oral administration vortioxetine and carvedilol in rats. Results suggested that the co-administration of vortioxetine and carvedilol results in a significant drug interaction in rats. SN - 1873-264X UR - https://www.unboundmedicine.com/medline/citation/27262994/Simultaneous_quantification_of_vortioxetine_carvedilol_and_its_active_metabolite_4_hydroxyphenyl_carvedilol_in_rat_plasma_by_UPLC_MS/MS:_Application_to_their_pharmacokinetic_interaction_study_ DB - PRIME DP - Unbound Medicine ER -