Determination of lansoprazole enantiomers in dog plasma by column‐switching liquid chromatography with tandem mass spectrometry and its application to a preclinical pharmacokinetic study |
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| Authors: | Hao Wang Yantong Sun Xiangjun Meng Bo Yang Jian Wang Jingkai Gu |
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| Affiliation: | 1. School of Life Sciences, Jilin University, Changchun, P.R. China;2. Research Center for Drug Metabolism, Jilin University, Changchun, P.R. China;3. School of Pharmaceutical Sciences, Jilin University, Changchun, P.R. China;4. Southeast Environmental Research Center, Florida International University, North Miami, FL, USA |
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| Abstract: | Lansoprazole, a selective proton pump inhibitor, has a chiral benzimidazole sulfoxide structure and is used for the treatment of gastric acid hypersecretory related diseases. To investigate its stereoselective pharmacokinetics, a column‐switching liquid chromatography with tandem mass spectrometry method was developed for the determination of lansoprazole enantiomers in dog plasma using (+)‐pantoprazole as an internal standard. After a simple protein precipitation procedure with acetonitrile, matrix components left behind after sample preparation were further eliminated from the sample by reversed‐phase chromatography on a C18 column. The fluent was fed to a chiral column for the separation of lansoprazole enantiomers. Baseline separation of lansoprazole enantiomers was achieved on a Chiralcel OZ‐RH column using acetonitrile/0.1% formic acid in water (35:65, v/v) as the mobile phase at 40°C. The linearity of the calibration curves ranged from 3 to 800 ng/mL for each enantiomer. Intra‐ and inter‐day precisions ranged from 2.1 to 7.3% with an accuracy of ±1.7% for (+)‐lansoprazole, and from 1.6 to 6.9% with an accuracy of ±3.5% for (–)‐lansoprazole, respectively. The validated method was successfully applied for the stereoselective pharmacokinetic study of lansoprazole in beagle dog after intravenous infusion. |
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| Keywords: | Column‐switching procedure Enantioselective pharmacokinetics Lansoprazole Liquid chromatography with tandem mass spectrometry |
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