A novel, precise, accurate and rapid HPLC-UV method was developed, optimised and fully validated for simultaneous estimation of pitavastatin (PIT) and candesartan (CAN) in rat plasma using telmisartan as an internal standard. Following liquid-liquid extraction of the analytes from plasma, chromatographic separation was accomplished on a Waters Reliant C18 column (4.6 × 250 mm, 5 µm) using ACN-5 mM Sodium acetate buffer (80:20, v/v; pH adjusted to 3.5 with acetic acid) as mobile phase at a flow rate of 0.8 mL/min and wavelength of 234 nm. The calibration curves were linear over the concentration ranges of 2-400 ng/mL and 3-400 ng/mL for pitavastatin and candesartan respectively. The method when validated as per US-FDA guidelines was found to be precise as well as accurate. Extraction recovery observed for both analytes was above 90% as well as reproducible and consistent. Stability studies showed the samples to be stable over a long period covering from sample collection to final analysis. The method was successfully applied to investigate pharmacokinetic interaction between PIT and CAN in wistar rats. The mean plasma concentration-time curves of PIT and CAN showed that single PIT as well as CAN show similar pharmacokinetic properties to those obtained when co-administrated with each other (P value > 0.05). Hence, there is no evidence for a potential drug-drug interaction between PIT and CAN. This information provides evidence for clinical rational use of CAN and PIT in cardiovascular patients.

开发了一种新颖，精确，准确和快速的HPLC-UV方法，对其进行了优化和充分验证，以替米沙坦为内标同时评估大鼠血浆中的匹伐他汀（PIT）和坎地沙坦（CAN）。从血浆中进行液-液萃取后，使用ACN-5 mM乙酸钠缓冲液（80：20，v / v；在pH值调节至3.5乙酸）作为流动相，流速为0.8 mL / min，波长为234 nm。匹伐他汀和坎地沙坦的校准曲线分别在2-400 ng / mL和3-400 ng / mL的浓度范围内呈线性。根据US-FDA指南验证的方法准确无误。两种分析物的萃取回收率均高于90％，并且具有可再现性和一致性。稳定性研究表明样品在从样品收集到最终分析的很长一段时间内都是稳定的。该方法已成功应用于研究wistar大鼠中PIT和CAN之间的药代动力学相互作用。PIT和CAN的平均血浆浓度-时间曲线表明，单个PIT和CAN的药代动力学特性与共同给药时获得的相似（P值> 0.05）。因此，没有证据表明PIT和CAN之间可能存在药物相互作用。该信息为心血管患者临床合理使用CAN和PIT提供了证据。