Simultaneous quantification of tizoxanide and tizoxanide glucuronide in mouse plasma by liquid chromatography-tandem mass spectrometry.
Nitazoxanide (NTZ) is a broad-spectrum antimicrobial agent. Tizoxanide (T) and tizoxanide glucuronide (TG) are the major circulating metabolites after oral administration of NTZ. A rapid and specific LC-MS/MS method for the simultaneous quantification of T and TG in mouse plasma was developed and validated. A simple acetonitrile-induced protein precipitation method was employed to extract two analytes and the internal standard glipizide from 50 μL of mouse plasma. The purified samples were resolved using a C18column with a mobile phase consisting of acetonitrile and 5 mm ammonium formate buffer (containing 0.05% formic acid) following a gradient elution. An API 3000 triple quadrupole mass spectrometer was operated under multiple reaction-monitoring mode with electrospray ionization. The precursor-to-product ion transitions m/z 264 → m/z 217 for T and m/z 440 → m/z 264 for TG were used for quantification. The developed method was linear in the concentration ranges of 1.0-500.0 ng/mL for T and 5.0-1000.0 ng/mL for TG. The intra- and inter-day precision and accuracy of the quality control samples at low, medium and high concentrations exhibited an RSD of <13.2% and the accuracy values ranged from -9.6 to 9.3%. We used this validated method to study the pharmacokinetics of T and TG in mice following oral administration of NTZ. Copyright © 2016 John Wiley & Sons, Ltd.
Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, 110016, People's Republic of China.
Jinqiu
J
Liu
Beijing Institute of Pharmacology and Toxicology, 27 Taiping Road, Beijing, 100850, People's Republic of China.
Fanhua
F
Meng
Evaluation and Research Center for Toxicology, Institute of Disease Control and Prevention, Academy of Military Medical Sciences, 20 Dongda Jie, Beijing, 100071, People's Republic of China.
Zhaofeng
Z
Li
Evaluation and Research Center for Toxicology, Institute of Disease Control and Prevention, Academy of Military Medical Sciences, 20 Dongda Jie, Beijing, 100071, People's Republic of China.
Lin
L
Yu
Evaluation and Research Center for Toxicology, Institute of Disease Control and Prevention, Academy of Military Medical Sciences, 20 Dongda Jie, Beijing, 100071, People's Republic of China.
Shuangqing
S
Peng
Evaluation and Research Center for Toxicology, Institute of Disease Control and Prevention, Academy of Military Medical Sciences, 20 Dongda Jie, Beijing, 100071, People's Republic of China. jifenguo@126.com.
Jifen
J
Guo
Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, 110016, People's Republic of China. xhy411@163.com.
Haiyan
H
Xu
D000818:Animals; D000977:Antiparasitic Agents / Q000097:blood* / Q000378:metabolism; D002853:Chromatography, Liquid / Q000379:methods; D020719:Glucuronides / Q000097:blood* / Q000378:metabolism; D057230:Limit of Detection; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009574:Nitro Compounds; D053719:Tandem Mass Spectrometry / Q000379:methods*; D013844:Thiazoles / Q000097:blood* / Q000378:metabolism
D000977:Antiparasitic Agents; D020719:Glucuronides; D009574:Nitro Compounds; D013844:Thiazoles; C104067:tizoxanide; C041747:nitazoxanide
LC-MS/MS; pharmacokinetics; tizoxanide; tizoxanide glucuronide