Departamento de Farmácia, Universidade Federal de Alfenas, 37130-000 Alfenas, MG, Brazil.
Talanta. 2009 Nov 15;80(1):236-41. doi: 10.1016/j.talanta.2009.06.060. Epub 2009 Jul 4.
This paper describes the optimization and validation of an analytical methodology for the determination of losartan potassium in capsules by HPLC using 2(5-1) fractional factorial and Doehlert designs. This multivariate approach allows a considerable improvement in chromatographic performance using fewer experiments, without additional cost for columns or other equipment. The HPLC method utilized potassium phosphate buffer (pH 6.2; 58 mmol L(-1))-acetonitrile (65:35, v/v) as the mobile phase, pumped at a flow rate of 1.0 mL min(-1). An octylsilane column (100 mm x 4.6mm i.d., 5 microm) maintained at 35 degrees C was used as the stationary phase. UV detection was performed at 254 nm. The method was validated according to the ICH guidelines, showing accuracy, precision (intra-day relative standard deviation (R.S.D.) and inter-day R.S.D values <2.0%), selectivity, robustness and linearity (r=0.9998) over a concentration range from 30 to 70 mg L(-1) of losartan potassium. The limits of detection and quantification were 0.114 and 0.420 mg L(-1), respectively. The validated method may be used to quantify losartan potassium in capsules and to determine the stability of this drug.
本文描述了一种通过 HPLC 用 2(5-1) 部分因子和 Doehlert 设计优化和验证用于测定胶囊中氯沙坦钾的分析方法。这种多元方法可以在不增加柱或其他设备成本的情况下，通过更少的实验显著改善色谱性能。HPLC 方法采用磷酸钾缓冲液（pH 6.2；58mmol L(-1))-乙腈（65:35，v/v）作为流动相，以 1.0mL min(-1)的流速泵送。使用 100mm×4.6mm i.d.、5μm 的辛基硅烷柱作为固定相，在 35°C 下保持。UV 检测在 254nm 处进行。该方法按照 ICH 指南进行了验证，显示了准确性、精密度（日内相对标准偏差（R.S.D.）和日间 R.S.D.值<2.0%）、选择性、稳健性和线性（r=0.9998），浓度范围为 30 至 70mg L(-1)的氯沙坦钾。检测限和定量限分别为 0.114 和 0.420mg L(-1)。验证后的方法可用于定量胶囊中的氯沙坦钾，并确定该药物的稳定性。
