Development and validation of a sensitive UHPLC-MS/MS method for quantitation of prucalopride in rat plasma and its application to pharmacokinetics study.
A rapid, sensitive, selective and accurate ultra high performance liquid chromatography with tandem mass spectrometry (UHPLC-MS/MS) method was developed and validated for the quantitation of prucalopride in rat plasma using carbamazepine as an internal standard (IS). Separation was achieved on a Waters ACQUITY UHPLC(®) HSS C18 column (2.1mm×50mm, 1.8μm) column with a gradient mobile phase consisting of acetonitrile-water (containing 0.1% formic acid) as mobile phase at a flow rate of 0.2mL/min. Prucalopride and IS were monitored using positive electrospray triple quadrupole mass spectrometer (Waters Xevo TQD) via multiple reaction monitoring (MRM) mode. The monitored transitions were set at m/z 367.99→195.89 and m/z 236.97→194.04 for prucalopride and IS, respectively. The achieved lower limit of quantitation was 0.1ng/mL. The validated method had an excellent linearity in the range of 0.1-100ng/mL (r>0.996). The intra- and inter-day precisions were both≤7.8% for prucalopride and IS, and the average intra- and inter-day accuracies ranged from -3.0% to 8.5%. Extraction recoveries at three levels QC concentrations were in the range of 90.0-110.0% for prucalopride and 99.6% for IS. Matrix effects were found to be acceptable. The validated assay was successfully applied to a pharmacokinetic study of prucalopride following oral administration of 0.25, 0.5, 1.0mg/kg to female and male rats respectively.
Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, No.1 Jianshe East Road, Henan Province, 450052, PR China.
Zhi
Z
Sun
Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, No.1 Jianshe East Road, Henan Province, 450052, PR China.
Lihua
L
Zuo
Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, No.1 Jianshe East Road, Henan Province, 450052, PR China.
Jian
J
Kang
Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, No.1 Jianshe East Road, Henan Province, 450052, PR China.
Lin
L
Zhou
Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, No.1 Jianshe East Road, Henan Province, 450052, PR China.
Mengmeng
M
Jia
Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, No.1 Jianshe East Road, Henan Province, 450052, PR China.
Zeyun
Z
Li
Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, No.1 Jianshe East Road, Henan Province, 450052, PR China.
Zhiheng
Z
Yang
Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, No.1 Jianshe East Road, Henan Province, 450052, PR China. Electronic address: zhangxiaojian_yxb@163.com.
Xiaojian
X
Zhang
Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, No.1 Jianshe East Road, Henan Province, 450052, PR China. Electronic address: zhenfeng1997@sina.com.
Zhenfeng
Z
Zhu
D000284:Administration, Oral; D000818:Animals; D001572:Benzofurans / Q000008:administration & dosage / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics*; D002138:Calibration; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004355:Drug Stability; D005260:Female; D008297:Male; D017207:Rats, Sprague-Dawley; D012015:Reference Standards; D015203:Reproducibility of Results; D053719:Tandem Mass Spectrometry / Q000379:methods*; D013997:Time Factors
D001572:Benzofurans; C406662:prucalopride
Pharmacokinetics; Prucalopride; Rat plasma; UHPLC–MS/MS