title: Simultaneous determination of oxiracetam and its degraded substance in rat plasma by HPLC-MS/MS and its application to pharmacokinetic study after a single high-dose intravenous administration.
abstract: A simple, rapid and sensitive reversed-phase ultra-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method was developed and validated for the simultaneous quantitative determination of oxiracetam and its degraded substance 4-hydroxy-2-oxo-1-pyrrolidine acetic acid (HOPAA) in rat plasma. After plasma samples were deproteinized with acetonitrile, the post-treatment samples were analyzed on a C18 column interfaced with a triple quadrupole tandem mass spectrometer in the positive electrospray ionization mode at a flow rate of 0.35ml/min. Piracetam was used as internal standard (IS). Multiple selected reaction monitoring was performed using the transitions m/z 159.00→141.94, 159.95→113.98 and 142.98→125.97 to quantify oxiracetam, HOPAA and IS, respectively. This method was validated over the concentration range of 25-2250μg/ml for oxiracetam (r(2)≥0.99) and 0.5-250μg/ml (r(2)≥0.99) for HOPAA. Intra-run and inter-run precision values of oxiracetam and HOPAA were less than 15% and accuracy was within 85-115% at all quality control levels. The average extraction recovery was 93.9% for oxiracetam and 95.6% for HOPAA, respectively. In conclusion, a simple, sensitive and specific HPLC-MS/MS method was successfully applied to the pharmacokinetic study in rats after an intravenous administration at a high dose of 2g/kg.
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, No. 103, Wenhua Road, Shenyang 110016, China.
authors.forename: Xinhuan
authors.initials: X
authors.lastname: Wan
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, No. 103, Wenhua Road, Shenyang 110016, China.
authors.forename: He
authors.initials: H
authors.lastname: Wang
authors.affiliation: Ningxia Kangya Pharmaceutical Co., Ltd, No. 6 Road, Yinchuang 750002, China.
authors.forename: Panqin
authors.initials: P
authors.lastname: Ma
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, No. 103, Wenhua Road, Shenyang 110016, China.
authors.forename: Long
authors.initials: L
authors.lastname: Xi
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, No. 103, Wenhua Road, Shenyang 110016, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Sun
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, No. 103, Wenhua Road, Shenyang 110016, China.
authors.forename: Zhonggui
authors.initials: Z
authors.lastname: He
authors.affiliation: School of Traditional Chinese Medicine, Shenyang Pharmaceutical University, No. 103, Wenhua Road, Shenyang 110016, China. Electronic address: zhangxr@vip.sina.com.
authors.forename: Xiangrong
authors.initials: X
authors.lastname: Zhang
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, No. 103, Wenhua Road, Shenyang 110016, China. Electronic address: lvj221@163.com.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Liu
mesh_terms: D061605:Administration, Intravenous; D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004355:Drug Stability; D016018:Least-Squares Analysis; D008297:Male; D011759:Pyrrolidines / Q000008:administration & dosage / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D011759:Pyrrolidines; C040619:oxiracetam
keywords: 4-Hydroxy-2-oxo-1-pyrrolidine acetic acid; HPLC-MS/MS; Oxiracetam; Pharmacokinetics.; Rat plasma; Simultaneous determination