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.

Pantoprazole, a proton pump inhibitor, is clinically used for the treatment of peptic diseases. An enantioselective LC-MS/MS method was developed and validated for the simultaneous determination of pantoprazole enantiomers in human plasma. Pantoprazole enantiomers and the internal standard were extracted from plasma using acetonitrile. Chiral separation was carried on a Chiralpak IE column using the mobile phase consisted of 10 mm ammonium acetate solution containing 0.1% acetic acid-acetonitrile (28 : 72, v/v). MS analysis was performed on an API 4000 mass spectrometer. Multiple reactions monitoring transitions of m/z 384.1→200.1 and 390.1→206.0 were used to quantify pantoprazole enantiomers and internal standard, respectively. For each enantiomer, no apparent matrix effect was found, the calibration curve was linear over 5.00-10,000 ng/mL, the intra- and inter-day precisions were below 10.0%, and the accuracy was within the range of -5.6% to 0.6%. This method was applied to the stereoselective pharmacokinetic studies in human after intravenous administration of S-(-)-pantoprazole sodium injections. No chiral inversion was observed during sample storage, preparation procedure and analysis. While R-(+)-pantoprazole was detected in human plasma with a slightly high concentration, which implied that S-(-)-pantoprazole may convert to R-(+)-pantoprazole in some subjects.

l-Valine, l-leucine, l-isoleucine, l-phenylalanine, and l-tyrosine are important proposed biomarkers for the early detection and diagnosis of type 2 diabetes. A simple and selective hydrophilic interaction chromatography with tandem mass spectrometry method was developed for the simultaneous determination of these amino acids in human serum, using stable isotope-labeled amino acids as internal standards. Chromatographic separation was carried out on a Syncronis HILIC column (150 mm × 2.1 mm, 5 μm) with the column temperature of 35°C and a mobile phase consisted of acetonitrile/120 mM ammonium acetate (89:11, v/v), and the run time was 11.0 min. The mass spectrometric analysis was performed using a QTRAP 5500 mass spectrometer coupled with an electrospray ionization source in positive ion mode. As these five amino acids are endogenous compounds in serum, we used the corresponding stable isotope-labeled amino acids to evaluate the matrix effect and recovery in serum. The matrix effect was 98.7-107.3%, and the recovery was 92.7-102.3%. Calibration curves spiked unlabeled amino acids in water were linear over the range of 0.200-100 μg/mL. The accuracy, inter-, and intraday precision were below 10.2%. Analytes were stable during the study. This assay method has been validated and applied to the early diagnosis research of type 2 diabetes.

The pharmacokinetics of fudosteine in healthy Chinese volunteers was investigated for the first time after single- and multiple-dose administration. Five male and five female volunteers were enrolled in this study. Each subject received 400 mg fudosteine capsules (the therapeutic dose) on day 1 after overnight fasting for the single-dose study and three times daily oral administration (400 mg) for 5 consecutive days until the sixth morning for the multiple-dose study. Serial blood samples were collected at specified time intervals up to 16 hours following the first and last doses of fudosteine. Plasma harvested from the blood was separated and analyzed for fudosteine levels by a validated high-performance liquid chromatography-electrospray ionization mass spectrometry (HPLC/ESI/MS) method employing percolumn derivatization with 9-fluorenylmethyl chloroformate (FMOC-Cl). Noncompartmental analysis was used for the calculation of the total area under the plasma concentration-time curve (AUC) from time zero to time infinity and the terminal half-life (t1/2) of fudosteine. The pharmacokinetic parameters for single- and multiple-dose administration were estimated as follows: Cmax amounted to 10.13+/-4.39 microg/mL and 11.75+/-6.51 microg/mL, tmax to 0.69+/-0.36 h and 0.53+/-0.12 h and t1/2 to 2.33+/-0.63 h and 2.40+/-0.37 h, respectively. No significant differences were found between single- and multiple-dose oral administration, although gender differences were observed.