title: Development and validation of a sensitive LC-MS/MS assay for the quantification of nizatidine in human plasma and urine and its application to pharmacokinetic study.
abstract: We developed and validated a high performance liquid chromatographic method coupled with triple quadrupole mass spectrometry for analysis of nizatidine in human plasma and urine. The biological samples were precipitated with methanol before separation on an Agilent Eclipse Plus C18 column (100mm×46mm, 5μm) with a mixture of methanol and water (95:5, plus 5mM ammonium formate) as the mobile phase at 0.5mL/min. Detection was performed using multiple reaction monitoring modes via electrospray ionization (ESI) at m/z 332.1→155.1 (for nizatidine) and m/z 335.1→155.1 (for [(2)H3]-nizatidine, the internal standard). The linear response range was 5-2000ng/mL and 0.5-80μg/mL for human plasma and urine, with the lower limits of quantification of 5ng/mL and 0.5μg/mL, respectively. The method was validated according to the biological method validation guidelines of the Food and Drug Administration and proved acceptable. This newly developed analytical method was successfully applied in a pharmacokinetic study following single oral administration of a 150mg nizatidine capsule in to 16 healthy Chinese subjects. Maximum and endpoint concentrations in plasma and urine were quantifiable, suggesting our method is appropriate for routine pharmacokinetic analysis.
authors.affiliation: Department of Pharmacy, Guangzhou Brain Hospital, Guangzhou Medical University, 36 Mingxin Road, Guangzhou 510370, China.
authors.forename: De-Wei
authors.initials: DW
authors.lastname: Shang
authors.affiliation: Department of Pharmacy, Guangzhou Brain Hospital, Guangzhou Medical University, 36 Mingxin Road, Guangzhou 510370, China.
authors.forename: Zhan-Zhang
authors.initials: ZZ
authors.lastname: Wang
authors.affiliation: Department of Pharmacy, Guangzhou Brain Hospital, Guangzhou Medical University, 36 Mingxin Road, Guangzhou 510370, China.
authors.forename: Xiao-Jia
authors.initials: XJ
authors.lastname: Ni
authors.affiliation: Department of Pharmacy, Guangzhou Brain Hospital, Guangzhou Medical University, 36 Mingxin Road, Guangzhou 510370, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Pharmacy, Guangzhou Brain Hospital, Guangzhou Medical University, 36 Mingxin Road, Guangzhou 510370, China.
authors.forename: Jin-Qing
authors.initials: JQ
authors.lastname: Hu
authors.affiliation: Department of Pharmacy, Guangzhou Brain Hospital, Guangzhou Medical University, 36 Mingxin Road, Guangzhou 510370, China.
authors.forename: Chang
authors.initials: C
authors.lastname: Qiu
authors.affiliation: Department of Pharmacy, Guangzhou Brain Hospital, Guangzhou Medical University, 36 Mingxin Road, Guangzhou 510370, China. Electronic address: wenyuguandede@163.com.
authors.forename: Yu-Guan
authors.initials: YG
authors.lastname: Wen
mesh_terms: D000328:Adult; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D005260:Female; D006635:Histamine H2 Antagonists / Q000097:blood* / Q000493:pharmacokinetics / Q000652:urine*; D006801:Humans; D008297:Male; D016567:Nizatidine / Q000097:blood* / Q000493:pharmacokinetics / Q000652:urine*; D012680:Sensitivity and Specificity; D053719:Tandem Mass Spectrometry / Q000379:methods*; D055815:Young Adult
chemical_list: D006635:Histamine H2 Antagonists; D016567:Nizatidine
keywords: LC–MS/MS; Nizatidine; Pharmacokinetics; Plasma; Urine