Enantioselective determination of (R)- and (S)-lansoprazole in human plasma by chiral liquid chromatography with mass spectrometry and its application to a stereoselective pharmacokinetic study.
A simple and enantioselective method was developed and validated for the simultaneous determination of (R)- and (S)-lansoprazole in human plasma by chiral liquid chromatography with tandem mass spectrometry. Lansoprazole enantiomers and internal standard (esomeprazole) were extracted from plasma using acetonitrile as protein precipitating agent. Baseline chiral separation was achieved within 9.0 min on a Chiralpak IC column (150 mm × 4.6 mm, 5 μm) with the column temperature of 30°C. The mobile phase consisted of 10 mM ammonium acetate solution containing 0.05% acetic acid/acetonitrile (50:50, v/v). The mass spectrometric analysis was performed using a QTrap 5500 mass spectrometer coupled with an electrospray ionization source in positive ion mode. The multiple reactions monitoring transitions of m/z 370.1→252.1 and 346.1→198.1 were used to quantify lansoprazole enantiomers and esomeprazole, respectively. For each enantiomer, no apparent matrix effect was found, the calibration curve was linear over 5.00-3000 ng/mL, the intra- and inter-day precisions were below 10.0%, and the accuracy was -3.8 to 3.3%. Analytes were stable during the study. No chiral inversion was observed during sample storage, preparation procedure and analysis. The method was applied to the stereoselective pharmacokinetic studies in human after intravenous administration of dexlansoprazole or racemic lansoprazole.
Research Division of Clinical Pharmacology, First Affiliated Hospital, Nanjing Medical University, Nanjing, China.
Luning
L
Sun
Department of Gastroenterology, First Affiliated Hospital, Nanjing Medical University, Nanjing, China.
Yang
Y
Cao
Department of Pharmacology, China Pharmaceutical University, Nanjing, China.
Huiwen
H
Jiao
Department of Pharmacology, China Pharmaceutical University, Nanjing, China.
Yunqian
Y
Fang
Department of Pharmacology, China Pharmaceutical University, Nanjing, China.
Zhicheng
Z
Yang
Research Division of Clinical Pharmacology, First Affiliated Hospital, Nanjing Medical University, Nanjing, China.
Mingliang
M
Bian
Research Division of Clinical Pharmacology, First Affiliated Hospital, Nanjing Medical University, Nanjing, China.
Hongwen
H
Zhang
Department of Pharmacology, China Pharmaceutical University, Nanjing, China.
Xiaojian
X
Gong
Research Division of Clinical Pharmacology, First Affiliated Hospital, Nanjing Medical University, Nanjing, China.
Yongqing
Y
Wang
D000897:Anti-Ulcer Agents / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D002853:Chromatography, Liquid / Q000379:methods*; D006801:Humans; D064747:Lansoprazole / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D013058:Mass Spectrometry / Q000379:methods*; D013237:Stereoisomerism
D000897:Anti-Ulcer Agents; D064747:Lansoprazole
Chiral liquid chromatography; Dexlansoprazole; Lansoprazole; Pharmacokinetics; Tandem mass spectrometry