title: Quantification of peramivir in dog plasma by liquid chromatography/tandem mass spectrometry employing precolumn derivatization.
abstract: Peramivir is a novel influenza neuraminidase inhibitor used for anti-influenza. In this article, a novel method was developed to determine peramivir in dog plasma using a derivatization treatment step to increase the retention time and enhance the signal intensity. The sample preparation consisted of a protein precipitation extraction followed by derivatization with 10M hydrochloric acid-methanol (10:90, v/v) and determined by liquid chromatography coupled with tandem mass spectrometry. The selected reaction monitoring mode of the positive ion was performed and the precursor to the product ion transitions of m/z 343→284 and m/z 299→152 were used to measure the derivative of peramivir and Ro 64-0802 (internal standard, an active metabolite of oseltamivir). The chromatographic separation was achieved using a ZORBAX RX-C8 (2.0mm×150mm×5μm) analytical column with an isocratic mobile phase composed of acetonitrile-water-formic acid (30:70:0.1, v/v/v, 0.2mL/min). The method was linear over a concentration range of 0.25-250ng/mL. The average intra-day/inter-day precision values were 4.04-8.17% and 3.02-7.08%, respectively, while the average accuracy value was 93.99-106.48%. This method has been successfully applied to the preclinical dog research of peramivir following intragastric administration.
authors.affiliation: Department of Pharmacy, Chinese PLA General Hospital, Beijing, China; Beijing Institute of Pharmacology and Toxicology, Beijing, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.affiliation: Beijing Institute of Pharmacology and Toxicology, Beijing, China. Electronic address: leeying1020@sina.com.
authors.forename: Ying
authors.initials: Y
authors.lastname: Li
authors.affiliation: Beijing Institute of Pharmacology and Toxicology, Beijing, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Wang
authors.affiliation: Beijing Institute of Pharmacology and Toxicology, Beijing, China.
authors.forename: Lili
authors.initials: L
authors.lastname: Wang
authors.affiliation: Beijing Institute of Pharmacology and Toxicology, Beijing, China.
authors.forename: Wu
authors.initials: W
authors.lastname: Zhong
authors.affiliation: Beijing Institute of Pharmacology and Toxicology, Beijing, China.
authors.forename: Jinxiu
authors.initials: J
authors.lastname: Ruan
authors.affiliation: Beijing Institute of Pharmacology and Toxicology, Beijing, China.
authors.forename: Zhenqing
authors.initials: Z
authors.lastname: Zhang
mesh_terms: D000146:Acids, Carbocyclic; D000818:Animals; D002853:Chromatography, Liquid / Q000379:methods*; D003517:Cyclopentanes / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D004285:Dogs; D004355:Drug Stability; D004951:Esterification; D006146:Guanidines / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D016018:Least-Squares Analysis; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D000146:Acids, Carbocyclic; D003517:Cyclopentanes; D006146:Guanidines; C414210:peramivir
keywords: Derivatization; Dog plasma; Influenza virus neuraminidase inhibitor; Liquid chromatography–tandem mass spectrometric method (LC–MS/MS); Peramivir