A rapid, accurate, and precise chiral Ultra fast liquid chromatography (UFLC) method was developed and validated for enantiomeric separation of racemic vildagliptin and <i>S</i>-vildagliptin according to t...A rapid, accurate, and precise chiral Ultra fast liquid chromatography (UFLC) method was developed and validated for enantiomeric separation of racemic vildagliptin and <i>S</i>-vildagliptin according to the guidelines of the International Conference on Harmonization (ICH). The chiral chromatographic separation was achieved with a mobile phase consisting of 20 mM borax buffer (pH 9.0 ± 0.05), ACN, and 0.1% Triethylamine (50:50:0.1, v/v/v) at a flow rate of 1 ml/min using a chiralcel OD-RH column, tris(3,5-dimethyl phenyl carbamate) (250 mm × 4.6 mm, 5 μm) column. The UFLC analysis was monitored at 210 nm. The method showed good linearity with a regression coefficient (r<sup>2</sup>) of 0.999 in the range of 1 - 12 μg/ml for <i>S</i>-vilda. The detection limit (LOD), quantitation limit (LOQ), and the average percentage recovery for <i>S</i>-vilda were found to be 0.024, 0.075 μg/mL, and 99.19% to 100.4%, respectively. The percentages of relative standard deviation (% RSD) for intra- and inter-day precision were found to be 0.346% and 0.364%, respectively. The developed method proved to be reproducible as % RSD was <2% and it had robustness within the acceptable limit. The percentage purity of pharmaceutical preparations of <i>S</i>-vilda was found to be 99.19 w/w. The proposed chiral method can be put in application for the enantiomeric purity determination of <i>S</i>-vilda formulations.展开更多
目的建立测定人血浆中维格列汀质量浓度的液相色谱-串联质谱(liquid chromatography tandem mass spectrometry,LC-MS/MS)联用方法,考察空腹条件下维格列汀片的人体药动学特征。方法血浆样品经蛋白沉淀法处理,采用稳定同位素标记^(13)C_...目的建立测定人血浆中维格列汀质量浓度的液相色谱-串联质谱(liquid chromatography tandem mass spectrometry,LC-MS/MS)联用方法,考察空腹条件下维格列汀片的人体药动学特征。方法血浆样品经蛋白沉淀法处理,采用稳定同位素标记^(13)C_(5)-^(15)N-维格列汀作为内标,采用Hypurity C_(18)(150 mm×2.1 mm,5μm)色谱柱分离,进行梯度洗脱,流动相为5 mmol·L^(-1)甲酸铵水溶液(A)-乙腈(B),流速为0.5 mL·min^(-1)。在正离子条件下选择多反应离子监测模式进行定量分析。将8名健康受试者采用随机双周期双交叉方式进行空腹试验,并通过WinNonlin 8.1软件计算药动学参数。结果人血浆中维格列汀在质量浓度1.11~534.00μg·L^(-1)内线性关系良好。批内和批间准确度偏差均在±15%以内,精密度相对标准偏差均小于15%。各基质内标归一化的基质因子相对标准偏差均小于5%,选择性、提取回收率、残留效应、稀释可靠性和稳定性均符合要求。结论所建立的方法符合生物样本分析要求,可用于人血浆中维格列汀质量浓度检测及其药动学研究。展开更多
文摘A rapid, accurate, and precise chiral Ultra fast liquid chromatography (UFLC) method was developed and validated for enantiomeric separation of racemic vildagliptin and <i>S</i>-vildagliptin according to the guidelines of the International Conference on Harmonization (ICH). The chiral chromatographic separation was achieved with a mobile phase consisting of 20 mM borax buffer (pH 9.0 ± 0.05), ACN, and 0.1% Triethylamine (50:50:0.1, v/v/v) at a flow rate of 1 ml/min using a chiralcel OD-RH column, tris(3,5-dimethyl phenyl carbamate) (250 mm × 4.6 mm, 5 μm) column. The UFLC analysis was monitored at 210 nm. The method showed good linearity with a regression coefficient (r<sup>2</sup>) of 0.999 in the range of 1 - 12 μg/ml for <i>S</i>-vilda. The detection limit (LOD), quantitation limit (LOQ), and the average percentage recovery for <i>S</i>-vilda were found to be 0.024, 0.075 μg/mL, and 99.19% to 100.4%, respectively. The percentages of relative standard deviation (% RSD) for intra- and inter-day precision were found to be 0.346% and 0.364%, respectively. The developed method proved to be reproducible as % RSD was <2% and it had robustness within the acceptable limit. The percentage purity of pharmaceutical preparations of <i>S</i>-vilda was found to be 99.19 w/w. The proposed chiral method can be put in application for the enantiomeric purity determination of <i>S</i>-vilda formulations.
