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
Abstract: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… Show more
“…The decision factors of chiral separation and analysis were the selection of chiral columns and the composition of the mobile phase . We attempted to separate (R)‐(+)‐ and (S)‐(−)‐rabeprazole on a Chiralpak IE column.…”
Section: Resultsmentioning
confidence: 99%
“…Fortunately, the Chiralpak IC column, with cellulose derivative immobilized stationary phase, has been successfully used to separate rabeprazole enantiomers using an analytical run time of 8 minutes. The use of 10 mM ammonium acetate keeps the stability of aqueous phase and ensures the reproducibility of retention time . The aqueous phase added 0.2% acetic acid enhanced ionization and improved sensitivity, which also results in a shorter analytical run time .…”
Section: Resultsmentioning
confidence: 99%
“…Methods used to evaluate the matrix effect followed the local standard operating procedures. Two sets of samples at concentrations of 1.20 and 320 ng·mL −1 were prepared to evaluate the matrix effect of each enantiomer and IS.…”
Section: Methodsmentioning
confidence: 99%
“…The chiral inversion of (R)‐(+)‐ and (S)‐(−)‐rabeprazole at low and high concentrations (1.20 and 320 ng·mL −1 ) are evaluated by making up mixtures with R/S ((R)‐(+)−/(S)‐(−)‐rabeprazole) ratios at 1:0 and 0:1. These samples were analyzed using the chiral LC‐MS/MS method at all of the abovementioned storage and handling conditions by detecting the appearance of the corresponding enantiomer …”
Section: Methodsmentioning
confidence: 99%
“…Carryover was investigated by comparing the peak area at the retention time of the analytes and the IS in double blank sample immediately following the injection of the upper limit of quantification (400 ng·mL −1 ) to that of the LLOQ sample. The value of carryover should be no more than 20% of analytes and 5% for the IS …”
Rabeprazole is an effective proton pump inhibitor to treat acid‐related diseases. To achieve the simultaneous determination of rabeprazole enantiomers in human plasma, a chiral LC‐MS/MS method was developed and validated. Acetonitrile including 0.1% ammonium were used as protein precipitating agent. Analytes were separated within 8 minutes on a Chiralpak IC column (4.6 mm × 150 mm, 5 μm). The mobile phase was 10 mM ammonium acetate including 0.2% acetic acid‐acetonitrile (35:65, v/v). An API 4000 mass spectrometer was used as detector for the analysis, and the multiple reactions monitoring transitions of m/z 360.1 → 242.2 and 346.1 → 198.1 were opted for quantifying rabeprazole enantiomers and internal standard. Matrix effects were not apparent for each enantiomer and internal standard (esomeprazole), the calibration curves were linear over the concentration of 0.500 to 400 ng·mL−1, the intra‐run precisions were below 5.4%, the inter‐run precisions were below 9.9%, and the accuracy was between −9.2% and 9.3%. There was no chiral inversion observed during sample storage, preparation procedure, and analysis, demonstrating that analytes were stable in this study. This method was applied to the stereoselective pharmacokinetic study of (R)‐(+)‐ and (S)‐(−)‐rabeprazole after oral administration of 10‐mg rabeprazole sodium enteric‐coated tablet in healthy Chinese subjects.
“…The decision factors of chiral separation and analysis were the selection of chiral columns and the composition of the mobile phase . We attempted to separate (R)‐(+)‐ and (S)‐(−)‐rabeprazole on a Chiralpak IE column.…”
Section: Resultsmentioning
confidence: 99%
“…Fortunately, the Chiralpak IC column, with cellulose derivative immobilized stationary phase, has been successfully used to separate rabeprazole enantiomers using an analytical run time of 8 minutes. The use of 10 mM ammonium acetate keeps the stability of aqueous phase and ensures the reproducibility of retention time . The aqueous phase added 0.2% acetic acid enhanced ionization and improved sensitivity, which also results in a shorter analytical run time .…”
Section: Resultsmentioning
confidence: 99%
“…Methods used to evaluate the matrix effect followed the local standard operating procedures. Two sets of samples at concentrations of 1.20 and 320 ng·mL −1 were prepared to evaluate the matrix effect of each enantiomer and IS.…”
Section: Methodsmentioning
confidence: 99%
“…The chiral inversion of (R)‐(+)‐ and (S)‐(−)‐rabeprazole at low and high concentrations (1.20 and 320 ng·mL −1 ) are evaluated by making up mixtures with R/S ((R)‐(+)−/(S)‐(−)‐rabeprazole) ratios at 1:0 and 0:1. These samples were analyzed using the chiral LC‐MS/MS method at all of the abovementioned storage and handling conditions by detecting the appearance of the corresponding enantiomer …”
Section: Methodsmentioning
confidence: 99%
“…Carryover was investigated by comparing the peak area at the retention time of the analytes and the IS in double blank sample immediately following the injection of the upper limit of quantification (400 ng·mL −1 ) to that of the LLOQ sample. The value of carryover should be no more than 20% of analytes and 5% for the IS …”
Rabeprazole is an effective proton pump inhibitor to treat acid‐related diseases. To achieve the simultaneous determination of rabeprazole enantiomers in human plasma, a chiral LC‐MS/MS method was developed and validated. Acetonitrile including 0.1% ammonium were used as protein precipitating agent. Analytes were separated within 8 minutes on a Chiralpak IC column (4.6 mm × 150 mm, 5 μm). The mobile phase was 10 mM ammonium acetate including 0.2% acetic acid‐acetonitrile (35:65, v/v). An API 4000 mass spectrometer was used as detector for the analysis, and the multiple reactions monitoring transitions of m/z 360.1 → 242.2 and 346.1 → 198.1 were opted for quantifying rabeprazole enantiomers and internal standard. Matrix effects were not apparent for each enantiomer and internal standard (esomeprazole), the calibration curves were linear over the concentration of 0.500 to 400 ng·mL−1, the intra‐run precisions were below 5.4%, the inter‐run precisions were below 9.9%, and the accuracy was between −9.2% and 9.3%. There was no chiral inversion observed during sample storage, preparation procedure, and analysis, demonstrating that analytes were stable in this study. This method was applied to the stereoselective pharmacokinetic study of (R)‐(+)‐ and (S)‐(−)‐rabeprazole after oral administration of 10‐mg rabeprazole sodium enteric‐coated tablet in healthy Chinese subjects.
Chiral separation in the class of proton pump inhibitors by chromatographic and electromigration techniques: An overviewProton pump inhibitors (PPIs) are benzimidazole-derivative chiral sulfoxides, frequently used in the treatment of gastric hyperacidity-related disorders. Due to their stereoselective metabolism, the eutomeric forms of PPIs can present a more advantageous pharmacokinetic profile by comparison with the distomers or racemates. Moreover, two representatives of the class are used in therapy both as racemates and as pure enantiomers (esomeprazole, dexlansoprazole). A relatively large number of enantioseparation methods employed for the stereoselective determination of PPIs from pharmaceutical, biological, and environmental matrices were published in the past three decades. The purpose of the current overview is to provide a systematic survey of the available chiral separation methods published since the introduction of PPIs in the therapy up to the present. Analytical and bioanalytical methods using different chromatographic and electromigration techniques reported for the enantioseparation of omeprazole, lansoprazole, pantoprazole, rabeprazole, ilaprazole, and tenatoprazole are included. The analytical conditions of the presented methods are summarized in three comprehensive tables, while a critical discussion of the applied techniques, possible mechanism of enantiorecognition, and future perspectives on the topic are also presented.
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