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.
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.
Wenzhou People's Hospital, Wenzhou 325000, China.
Yi
Y
Huang
The Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, China.
Shuangli
S
Zheng
Medical College of Henan University of Science and Technology, Luoyang 471003, China.
Yongyang
Y
Pan
Medical College of Henan University of Science and Technology, Luoyang 471003, China.
Tao
T
Li
The Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, China. Electronic address: xuzhisheng1111@163.com.
Zhi-Sheng
ZS
Xu
The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China. Electronic address: wzshaomengmeng@163.com.
Meng-Meng
MM
Shao
D000319:Adrenergic beta-Antagonists / Q000097:blood* / Q000493:pharmacokinetics*; D000818:Animals; D000928:Antidepressive Agents / Q000097:blood* / Q000493:pharmacokinetics*; D002138:Calibration; D002227:Carbazoles / Q000097:blood* / Q000493:pharmacokinetics*; D000077261:Carvedilol; D002851:Chromatography, High Pressure Liquid; D003975:Diazepam / Q000737:chemistry; D004347:Drug Interactions; D008297:Male; D010879:Piperazines / Q000097:blood* / Q000493:pharmacokinetics*; D011412:Propanolamines / Q000097:blood* / Q000493:pharmacokinetics*; D011786:Quality Control; D051381:Rats; D017207:Rats, Sprague-Dawley; D012015:Reference Standards; D015203:Reproducibility of Results; D021241:Spectrometry, Mass, Electrospray Ionization; D013440:Sulfides / Q000097:blood* / Q000493:pharmacokinetics*; D053719:Tandem Mass Spectrometry; D000078784:Vortioxetine
C000618271:4-hydroxyphenyl carvedilol; D000319:Adrenergic beta-Antagonists; D000928:Antidepressive Agents; D002227:Carbazoles; D010879:Piperazines; D011412:Propanolamines; D013440:Sulfides; D000077261:Carvedilol; D000078784:Vortioxetine; D003975:Diazepam
4-hydroxyphenyl carvedilol; Carvedilol; Pharmacokinetics; UPLC–MS/MS; Vortioxetine