Development and validation of HPLC‐MS/MS method for the determination of lixivaptan in mouse plasma and its application in a pharmacokinetic study. (16th June 2017)

• Record Type: Journal Article
• Authors: Kadi, Adnan A.; Alrabiah, Haitham; Attwa, Mohamed W.; Attia, Sabry; Mostafa, Gamal A. E.
• Is Part Of: Biomedical chromatography. Volume 31:Number 11(2017:Nov.)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2017-06-16
• Subjects: LC‐MS/MS -- lixivaptan -- mouse plasma -- pharmacokinetic; Chromatographic analysis -- Periodicals; Biology -- Periodicals; Medicine -- Periodicals; Biology -- Periodicals; Chromatography -- methods -- Periodicals; Medicine -- Periodicals; 543.089
• DOI: 10.1002/bmc.4007
• Languages: English
• ISSNs: 0269-3879

Abstract

Abstract: The aim of the present study was to develop a simple, sensitive and accurate liquid chromatography–electrospray ionization tandem mass spectrometry (ESI‐MS/MS) method for the determination of lixivaptan (LIX) in mouse plasma using vildagliptin as the internal standard (IS). A precipitation procedure was used for the extraction of LIX and vildagliptin from mouse plasma. Chromatographic separation of LIX was achieved using a C18 analytical column (50 × 2.1 mm, 1.8 μm) at 25°C. The mobile phase comprised acetonitrile and ammonium formate (10 mm, pH 3.1; 40:60, v /v) pumped at a flow rate of 0.3 mL min −1 . A tandem mass spectrometer with an electrospray ionization source was used to perform the assay. Quantification of LIX at m/z 290 → 137 and IS at 154 → 97 was attained through multiple reaction monitoring. The investigated method was authenticated following the bio‐analytical method of validation guidelines of the US Food and Drug Administration. The developed method showed a good linearity over the concentration range from 5 to 500 ng mL −1, and the calibration curve was linear ( r = 0.9998). The mean recovery of LIX from mouse plasma was 99.2 ± 0.68%. All validation parameters for LIX were within the levels required for acceptance. The proposed method was effectively used for a pharmacokinetic study of LIX in mouse plasma.