Simultaneous determination of parecoxib sodium and its active metabolite valdecoxib in rat plasma by UPLC-MS/MS and its application to a pharmacokinetic study after intravenous and intramuscular administration.
In this study, we developed and validated a new, rapid, specific and sensitive ultra-performance liquid chromatography-tandem mass spectrometric (UPLC-MS/MS) method to simultaneously determine parecoxib sodium (PX) and its active metabolite, valdecoxib (VX), in rat plasma. Plasma samples were prepared by plasma protein precipitation combined with a liquid-liquid extraction method. The separation was carried out on a Kinetex C18 column (2.1mm×50mm, 2.6μm) with a gradient elution using methanol (A) and a 2mM ammonium acetate aqueous solution (B). The analysis was performed in less than 3min with a flow rate of 0.2mL/min. Ketoprofen was used as an internal standard (IS). Mass spectrometric detection was conducted with a triple quadrupole detector equipped with electrospray ionization in the negative ion mode (ESI(-)) using multiple reaction monitoring (MRM). The calibration curves were linear over the concentration ranges of 5-4000ng/mL for PX and 5-2000ng/mL for VX with all correlation coefficients greater than 0.998. The intra- and inter-day relative standard deviations (RSD) for both analytes were within 15% and the accuracy was within 85-115% at all quality control levels. The mean extraction recoveries for all analytes obtained from three concentrations of QC plasma samples were more than 89.0% efficient. Selectivity, matrix effect, dilution integrity and stability were also validated. The method was successfully used to investigate the pharmacokinetics of PX and VX in rat plasma after intravenous and intramuscular administration of PX.
Department of Biopharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Wenhua Road, Shenyang 110016, China.
Meina
M
Liu
Department of Pharmaceutical Analysis, School of Pharmacy, Shenyang Pharmaceutical University, Wenhua Road, Shenyang 110016, China.
Qiuyang
Q
Yu
Department of Biopharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Wenhua Road, Shenyang 110016, China.
Ping
P
Li
Department of Biopharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Wenhua Road, Shenyang 110016, China.
Meng
M
Zhu
Department of Biopharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Wenhua Road, Shenyang 110016, China.
Mingming
M
Fang
Department of Biopharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Wenhua Road, Shenyang 110016, China.
Bingjun
B
Sun
Department of Biopharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Wenhua Road, Shenyang 110016, China.
Mengchi
M
Sun
Department of Biopharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Wenhua Road, Shenyang 110016, China.
Yinghua
Y
Sun
Department of Pharmaceutical Analysis, School of Pharmacy, Shenyang Pharmaceutical University, Wenhua Road, Shenyang 110016, China.
Peng
P
Zhang
Department of Biopharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Wenhua Road, Shenyang 110016, China.
Zhonggui
Z
He
Department of Biopharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Wenhua Road, Shenyang 110016, China.
Jin
J
Sun
Department of Biopharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Wenhua Road, Shenyang 110016, China.
Yongjun
Y
Wang
Department of Biopharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Wenhua Road, Shenyang 110016, China. Electronic address: lvj221@163.com.
Xiaohong
X
Liu
D061605:Administration, Intravenous; D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D007273:Injections, Intramuscular; D007555:Isoxazoles / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics; D016014:Linear Models; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013449:Sulfonamides / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics; D053719:Tandem Mass Spectrometry / Q000379:methods*; D000096926:Benzenesulfonamides
D007555:Isoxazoles; D013449:Sulfonamides; C406224:valdecoxib; D000096926:Benzenesulfonamides; C409945:parecoxib
Metabolite; Parecoxib sodium; Pharmacokinetics; Rat plasma; UPLC–MS/MS; Valdecoxib