title: Development and Validation of a Sensitive and Specific LC-MS-MS Method for the Determination of Acotiamide in Rat Plasma.
abstract: Acotiamide is a new prokinetic drug that is used to treat functional dyspepsia (FD). A sensitive and specific LC-MS-MS method has been developed and validated for the analysis of acotiamide in rat plasma. The assay involved a simple protein precipitation (PPT) step with methanol-acetonitrile (50:50, v/v) and a gradient elution using a mobile phase consisting of water containing 0.1% formic acid and methanol containing 0.1% formic acid. The analytes were chromatographed on a reverse-phase Agilent Zorbax XDB C18 column (2.1 mm × 50 mm, 3.5 μm) with a flow rate of 0.50 mL/min. The analytes were monitored by tandem-mass spectrometry with positive electrospray ionization. The precursor-product transitions (m/z) in the positive ion mode were 451.4 → 271.3 and 386.2 → 122.2 for acotiamide and buspirone (internal standard, IS), respectively. The assay was shown to be linear over the range of 0.10-200 ng/mL, with a lower limit of quantification of 0.10 ng/mL. The method was shown to be reproducible and reliable with the inter- and intra-batch accuracy and precision were within ±15%. The assay has been successfully used for pharmacokinetic evaluation of acotiamide after intravenous and oral administration of 10 mg/kg acotiamide in rats. The oral absolute bioavailability (F) of acotiamide in rats was estimated to be 38.4 ± 13.5% with an elimination half-life (t1/2) value of 9.11 ± 0.40 h.
authors.affiliation: Department of Pharmacy, The Affiliated Hospital of Qingdao University, Qingdao 266003, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.affiliation: Clinical Physiology Research Center, Capital Institute of Pediatrics, Beijing 100020, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Huang
authors.affiliation: Department of Pharmacy, The Affiliated Hospital of Qingdao University, Qingdao 266003, China.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Pharmacy, The Affiliated Hospital of Qingdao University, Qingdao 266003, China.
authors.forename: Haijun
authors.initials: H
authors.lastname: Qu
authors.affiliation: Department of Pharmacy, The Affiliated Hospital of Qingdao University, Qingdao 266003, China.
authors.forename: Meijuan
authors.initials: M
authors.lastname: Sun
authors.affiliation: Department of Pharmacy, The Affiliated Hospital of Qingdao University, Qingdao 266003, China zhaozhenhuan828@sina.com.
authors.forename: Zhenhuan
authors.initials: Z
authors.lastname: Zhao
mesh_terms: D000818:Animals; D001549:Benzamides / Q000032:analysis / Q000097:blood*; D001774:Blood Chemical Analysis / Q000379:methods*; D002853:Chromatography, Liquid; D057230:Limit of Detection; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D053719:Tandem Mass Spectrometry; D013844:Thiazoles / Q000032:analysis / Q000097:blood*
chemical_list: D001549:Benzamides; D013844:Thiazoles; C410959:Z 338