Biopharmaceutical Research, Suven Life Sciences Ltd., Serene Chambers, Road - 5, Avenue - 7, Banjara Hills, Hyderabad 500034, India.
J Pharm Biomed Anal. 2013 Feb 23;74:227-34. doi: 10.1016/j.jpba.2012.10.020. Epub 2012 Oct 23.
A simple and rapid LC-MS/MS method was developed and validated for the quantification of epalrestat, an aldose reductase inhibitor for the treatment of diabetic neuropathy. Following protein precipitation epalrestat and IS were eluted with 10mM ammonium acetate and acetonitrile using a rapid gradient program on reverse phase column. Multiple reaction monitoring mode was used to monitor the transitions of m/z 318→58 for epalrestat and m/z 410→348 for the IS. The assay exhibited a linear dynamic range of 2-5,000 ng/mL for epalrestat in rat plasma. Acceptable precision and accuracy were obtained for concentrations over the standard curve range. The within batch accuracy was in the range of 101.3-108.0% with precision in the range of 3.0-12.3%. All the other validation parameters were within the acceptable limits. Validated method was applied to analyze rat plasma samples obtained from a pharmacokinetic study. After oral administration of epalrestat at 10mg/kg to wistar rats (n=3) mean C(max), AUC(0-24) (ngh/mL) and t(1/2) were found to be 4077 ± 1327 ng/mL, 8989 ± 1590 ngh/mL and 2.9 ± 1.4h, respectively. Bioavailability was found to be 90 ± 14% for epalrestat in male wistar rats.
建立并验证了一种用于测定醛糖还原酶抑制剂依帕司他的 LC-MS/MS 分析方法，用于治疗糖尿病周围神经病变。蛋白沉淀后，依帕司他和内标（IS）采用反相柱快速梯度洗脱，以 10mM 乙酸铵和乙腈洗脱。采用多反应监测模式监测 m/z 318→58（依帕司他）和 m/z 410→348（IS）的离子跃迁。在大鼠血浆中，依帕司他的测定线性范围为 2-5000ng/mL。在标准曲线范围内，可获得可接受的精密度和准确度。批内准确度在 101.3-108.0%范围内，精密度在 3.0-12.3%范围内。所有其他验证参数均在可接受范围内。验证后的方法用于分析来自药代动力学研究的大鼠血浆样品。在雄性 Wistar 大鼠（n=3）中以 10mg/kg 口服给予依帕司他后，发现 C(max)、AUC(0-24)（ng·h/mL）和 t(1/2)分别为 4077±1327ng/mL、8989±1590ng·h/mL 和 2.9±1.4h。依帕司他在雄性 Wistar 大鼠中的生物利用度为 90±14%。
