Development of an UPLC-MS/MS micromethod for quantitation of cinitapride in plasma and its application in a pharmacokinetic interaction trial

• Published in: Bioanalysis Vol. 9; no. 6; pp. 569 - 579
• Main Authors: Marcelín-Jiménez, Gabriel, Contreras, Leticia, Esquivel, Javier, Ávila, Óscar, Batista, Dany, Ángeles, Alionka P, García-González, Alberto
• Format: Journal Article
• Language: English
• Published: England Future Science Ltd 01.03.2017
• Subjects: Administration, Oral; Adolescent; Adult; Area Under Curve; Benzamides - administration & dosage; Benzamides - blood; Benzamides - pharmacokinetics; Calibration; Chromatography, High Pressure Liquid - instrumentation; Chromatography, High Pressure Liquid - methods; cinitapride; Cross-Over Studies; gastroesophageal reflux; Healthy Volunteers; HPLC-MS; Humans; Limit of Detection; Liquid-Liquid Extraction; Middle Aged; Reference Standards; Sensitivity and Specificity; simethicone; Spectrometry, Mass, Electrospray Ionization - instrumentation; Spectrometry, Mass, Electrospray Ionization - methods; Tandem Mass Spectrometry - instrumentation; Tandem Mass Spectrometry - methods; Young Adult; HPLC–MS; simethicone; gastroesophageal reflux; cinitapride
• ISSN: 1757-6180; 1757-6199
• DOI: 10.4155/bio-2016-0210

Cinitapride (CIN) is a benzamide-derived molecule used for the treatment of gastroesophageal reflux and dyspepsia. Its pharmacokinetics are controversial due to the use of supratherapeutic doses and the lack of sensitive methodology. Therefore, a sensitive and accurate micromethod was developed for its quantitation in human plasma. CIN was extracted from 300 µl of heparinized plasma by liquid-liquid extraction using cisapride as internal standard, and analyzed with an ultra performance liquid chromatograph employing positive multiple-reaction monitoring-MS. The method proved to be rapid, accurate and stable within a range between 50 and 2000 pg/ml and was successfully validated and applied in a pharmacokinetic interaction trial, where it was demonstrated that oral co-administration of simethicone does not modify the bioavailability of CIN.