Linagliptin is a highly specific, long‐acting inhibitor that is used as an orally administrable agent for type‐2 diabetes treatment. Because only the R‐enantiomer is of clinical use, we developed a ...capillary electrophoresis method for the determination of the enantiomeric impurity of this compound. Carboxymethyl‐β‐cyclodextrin was selected as the chiral selector for the separation of linagliptin enantiomers. Design of experiments and desirability functions were used for the analytical optimization, which was focused on understanding and improving the electrophoretic process. The effects of significant parameters (background electrolyte concentration and pH, cyclodextrin concentration, temperature, and voltage) were thoroughly investigated. The complete separation of linagliptin and its enantiomeric impurity with baseline resolution was achieved within 10 min on an uncoated fused‐silica capillary (50 μm inner diameter, 365 μm outer diameter, 64.5/56 cm in total/ effective length) maintained at 25°C, under an applied voltage of 28.0 kV. The background electrolyte contained 70 mM sodium acetate and 4.7 mM carboxymethyl‐β‐cyclodextrin, and the pH was adjusted to 6.10. The method was validated, and a limit of quantitation of 0.05% for the impurity was estimated.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
A simple and reliable high‐performance liquid chromatography method was developed to determine the enantiomeric impurity of tenofovir disoproxil fumarate, an orally bioavailable prodrug of tenofovir, ...commonly used for the treatment of human immunodeficiency virus and hepatitis B. Tenofovir disoproxil and its enantiomer, were completely separated on a Chiralpak IC column (3 μm, 100 × 4.6 mm, i.d.). The chiral separation was achieved using a mobile phase containing n‐hexane, ethanol, methanol, and triethylamine 65/25/10/0.1 (v/v/v/v) at a flow rate of 0.6 mL/min. Ideally, the reversal of enantiomer elution order was achieved on the Chiralpak IC column, to allow the elution of the minor enantiomeric impurity before the major component. Moreover, the proposed method was able to discriminate the active ingredient from the related substances available in the tenofovir disoproxil fumarate raw materials. These compounds were isolated and structurally elucidated by MS and nuclear magnetic resonance. Based on the spectral data, the structures of related substances were confirmed as tenofovir isoproxil monoester and fumaric acid. The high‐performance liquid chromatography method was optimized by the design of experiment approach and successfully validated following the International Conference on Harmonization guideline. Proposed method was effectively applied for the quantification of enantiomeric impurity in tenofovir disoproxil fumarate raw materials.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
A simple, cost‐effective, and greener HPLC method was investigated to determine 14 β‐lactams. To achieve this, various strategies were implemented such as the use of an aqueous mobile phase, ionic ...liquids, or an alternative organic solvent. Preliminary experiments were conducted using “one‐factor‐at‐a‐time” to identify the significant factors affecting chromatographic performance. The experimental design (central composite design) was then applied to thoroughly examine the effects of the key factors and exploit them to achieve optimal HPLC condition. The developed method was less hazardous and improved the retention and peak shape, compared with other conventional methods. The optimized assay condition was validated according to the ICH guidelines and effectively applied for the quantification of some β‐lactams in various formulations. These results imply that this novel HPLC method can be employed for routine analyses of some β‐lactams in pure drug and commercial formulations.
Combination of Green analytical chemistry and Experimental design in the determination of β‐lactams.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Rabeprazole is one of the latest proton-pump inhibitors used for treatment of several gastrointestinal disorders. For therapeutic applications, rabeprazole has been administered as a mixture of R-(+) ...and S-(−) enantiomers. Owing to pharmacological and toxicological differences between stereoisomers, chiral recognition has now become an integral part of drug research and development. A simple and rapid liquid chromatographic method for enantioselective separation and determination of R-(+) and S-(−) enantiomers of rabeprazole in bulk drug and pharmaceutical formulations was developed. Chiralpak IC (150 × 4.6 mm, 5 μm) column and μmobile phase containing hexane:ethanol:ethylenediamine (30:70:0.05 v/v) in an isocratic mode yielded baseline separation with resolution greater than 6.0 at 35 °C. Effects of additives and n-hexane were evaluated. Optimized condition was validated as per ICH guidelines. The method has good linearity, high sensitivity with LOD was 0.01 μg/mL and LOQ was 0.03 μg/mL for both enantiomers. Intra-day precision varied between 0.44 and 1.79% for S-(−) enantiomer, 0.65 and 1.97% for R-(+) enantiomer. Relative standard deviations of inter-day precision were less than 1.81% for both enantiomers. The percentage recovery for both enantiomers of rabeprazole ranged between 99.81 and 101.95%, 98.82 and 101.36% in material and tablets, respectively. The method was successfully applied to determine content of each enantiomer in commercial tablets.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Capillary zone electrophoresis was successfully applied to the enantiomeric purity determination of dexlansoprazole using sulfobutyl ether-β-cyclodextrin and methyl-β-cyclodextrin as chiral ...selectors. Separations were carried out in a 50 μm, 64/56 cm fused-silica capillary. The optimized conditions included 90 mM phosphate buffer, pH 6.0, containing 30 mM sulfobutyl ether-β-cyclodextrin, 20 mM methyl-β-cyclodextrin as background electrolyte, an applied voltage of 25 kV and a temperature of 16 °C, detection was at 280 nm. The assay was validated for the S-(−)-lansoprazole in the range of 0.2–1.0%. The limit of detection was 0.07%, the limit of quantitation was 0.20%, relative to a total concentration of 4.0 mg mL
−1
. Intra-day precision varied between 1.72 and 2.07%. Relative standard deviations of inter-day precision ranged between 1.62 and 1.96% for peak area ratio. The assay was applied for the determination of the chiral purity of dexlansoprazole capsules. Recovery in capsules was ranged between 101.7 and 103.1%.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
A simple, sensitive, and rapid assay based on hydrophilic interaction liquid chromatography (HILIC) with tandem mass spectrometry was developed and validated for the simultaneous determination of ...metformin and 13 other oral antihyperglycaemic drugs in human urine using metoprolol as an internal standard. A simple sample clean-up procedure using the “dilute and shoot” approach enabled fast and reliable analysis. Chromatographic separation was performed on a HILIC column using an elution gradient of mobile phase A, composed of 1 mM ammonium formate (pH 5), and mobile phase B, composed of acetonitrile, at a flow rate of 0.35 mL/min. Quantitation was performed on a triple quadrupole mass spectrometer operated in multiple reaction monitoring mode by using electrospray ionization in positive ion mode. The total chromatographic run time was 20 min. Calibration curves for each analyte were linear over concentration ranges of 2–300, 5–400, or 20–500 ng/mL, with a coefficient of determination above 0.99. The method was validated for selectivity, sensitivity, recovery, linearity, accuracy and precision, system suitability, robustness, and stability. Inter-batch and intra-batch coefficients of variation across four validation runs were ≤ 13.62%. The present method was successfully applied for the analysis of metformin and nateglinide in urine samples after their oral administration to healthy human subjects under fasted conditions.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
An innovative, simple, and rapid assay method based on liquid chromatography coupled with tandem mass spec- trometry (LC-MS/MS) was developed and validated for the simultaneous determination of eight ...statin drugs in human urine. A simple sample clean-up procedure using the “dilute and shoot” (DAS) approach enabled a fast and reliable analysis. The influ- ence of the dilution factor was investigated to ensure detectability and reduce the matrix effect. Chromatographic separation was performed on a Phenomenex Kinetex C18 column (50 × 3.0 mm i.d., 2.6 µm) using an elution gradient of mobile phase A com- posed of 0.1% acetic acid, and mobile phase B composed of acetonitrile, at a flow rate of 0.35 mL/min. Quantitation was per- formed on a triple quadrupole mass spectrometer operated in multiple reaction monitoring (MRM) mode using electrospray ionization in positive ion mode. The total chromatographic run time was 15 min. The method was validated for selectivity, sen- sitivity, recovery, linearity, accuracy, precision, and stability. The present method was successfully applied to the analysis of Rosuvastatin in urine samples after oral administration to healthy human subjects. KCI Citation Count: 0
An innovative, simple, and rapid assay method based on liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) was developed and validated for the simultaneous determination of eight ...statin drugs in human urine. A simple sample clean-up procedure using the "dilute and shoot" (DAS) approach enabled a fast and reliable analysis. The influence of the dilution factor was investigated to ensure detectability and reduce the matrix effect. Chromatographic separation was performed on a Phenomenex Kinetex C18 column ($50{\times}3.0mm$ i.d., $2.6{\mu}m$) using an elution gradient of mobile phase A composed of 0.1% acetic acid, and mobile phase B composed of acetonitrile, at a flow rate of 0.35 mL/min. Quantitation was performed on a triple quadrupole mass spectrometer operated in multiple reaction monitoring (MRM) mode using electrospray ionization in positive ion mode. The total chromatographic run time was 15 min. The method was validated for selectivity, sensitivity, recovery, linearity, accuracy, precision, and stability. The present method was successfully applied to the analysis of Rosuvastatin in urine samples after oral administration to healthy human subjects.
Coptidis Rhizoma (CR) has been used widely in traditional medicine to treat common diseases. This study aimed to develop a high-sensitivity liquid chromatography-tandem mass (LC-MS) spectrometry ...method for the evaluation of the pharmacokinetics of a new natural product that contain CR extract with the main bioactive compound, berberine, at trace concentrations. Human plasma samples were pretreated with methanol by a protein precipitation method. Berberine was analyzed on a Kinetex C18 column (2.1 mm × 50 mm, 100 Å, 1.7 µm) using a mobile phase of 10 mM ammonium formate/0.1% formic acid in water (A) and acetonitrile (B) (50:50, v/v) with a flow rate of 0.25 mL/min. The analyte was detected by using electrospray ionization in positive mode with multiple reaction monitoring (MRM). The method was sensitive, with a lower limit of quantification of 1 pg/mL, which has not been previously obtained. The method was validated (over the range of 1–50 pg/mL) and applied successfully for the pharmacokinetic study of human plasma samples. KCI Citation Count: 0
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