J Pharm Pharm Sci. 2020;23:289-303. doi: 10.18433/jpps30912.
A simple, rapid, sensitive, and reliable HPLC method with UV detection was developed and validated for simultaneous quantitation of docetaxel and celecoxib and paclitaxel for dissolution characterization and pharmacokinetic studies.
The HPLC assay was performed isocratically on a reversed-phase C18 μ-Bondapack column using a mobile phase of acetonitrile:water (45:55, v/v) at a flow rate of 1.2 mL/min, and the analytes were detected at 230 nm. Paclitaxel was used as an internal standard for analysis of plasma samples following simple liquid-liquid extraction with n-hexane:isoamyl alcohol (97:3). The method was validated for specificity, linearity, sensitivity, precision, accuracy, robustness, and in vitro-in vivo application.
The retention times for docetaxel, paclitaxel, and celecoxib were 10.94, 12.4, and 16.81 min, respectively. The standard curves covering 0.1-1 μg/mL and 0.05-4 μg/mL were linear using dissolution medium and rat plasma, respectively. The limit of quantitation of the method was 50 ng/mL using 100 μL of rat plasma sample and injection of 50 μL of the residue. Within- and between-day precision and accuracy did not exceed 16.86% and 12.10%, respectively. This validated method was successfully used to quantify docetaxel and celecoxib simultaneously in the release study of docetaxel- celecoxib -loaded porous microparticles and pharmacokinetics studies. The methods were found to be simple, specific, precise, accurate, and reproducible. In this study, paclitaxel was used as the internal standard while dexamethasone, flutamide, and budesonide proved suitable alternative as an internal standard.
Since docetaxel and celecoxib could be co-administered for the treatment of a wide range of cancers such as non-small cell lung carcinoma, the developed method is particularly advantageous for routine therapeutic drug monitoring and pharmacokinetic studies of these drugs.
建立并验证了一种简单、快速、灵敏、可靠的 HPLC-UV 法，用于同时定量测定多西他赛、塞来昔布和紫杉醇，以进行溶出度特征和药代动力学研究。
采用反相 C18 μ-Bondapack 柱，以乙腈-水（45:55，v/v）为流动相，在等度条件下进行 HPLC 分析，流速为 1.2 mL/min，检测波长为 230nm。以紫杉醇为内标，采用正己烷-异戊醇（97:3）进行简单的液-液萃取，用于分析血浆样品。该方法经过特异性、线性、灵敏度、精密度、准确度、稳健性和体内-体外应用验证。
多西他赛、紫杉醇和塞来昔布的保留时间分别为 10.94、12.4 和 16.81min。使用溶出介质和大鼠血浆分别得到 0.1-1μg/mL 和 0.05-4μg/mL 的标准曲线均呈线性。使用 100μL 大鼠血浆样品和进样 50μL 残渣，方法的定量下限为 50ng/mL。日内和日间精密度和准确度均不超过 16.86%和 12.10%。该验证方法成功用于载多西他赛-塞来昔布多孔微球的释放研究和药代动力学研究中同时定量测定多西他赛和塞来昔布。该方法简单、特异、精密、准确且重现性好。在本研究中，紫杉醇被用作内标，而地塞米松、氟他胺和布地奈德被证明是合适的替代内标。
由于多西他赛和塞来昔布可联合用于治疗多种癌症，如非小细胞肺癌，因此所建立的方法特别有利于这些药物的常规治疗药物监测和药代动力学研究。
