Pathak Ashutosh, Rajput Sadhana J
The Maharaja Sayajirao University of Baroda, Centre of Relevance and Excellence in Novel Drug Delivery Systems, Pharmacy Department, Quality Assurance Laboratory, G.H. Patel Building, Donor's Plaza, Fatehgunj, Vadodara, Gujarat, India 390 002.
J AOAC Int. 2008 Nov-Dec;91(6):1344-53.
The objective of the current study was to develop a validated stability-indicating high-performance liquid chromatographic method for alprazolam and sertraline in combined dosage forms. The method was validated by subjecting the drugs to forced decomposition under hydrolysis, oxidation, photolysis, and thermal stress conditions prescribed by the International Conference on Harmonization. The drugs were successfully separated from major and minor degradation products on a reversed-phase C18 column by using 75 mM potassium dihydrogen phosphate buffer (pH 4.3)-acetonitrile-methanol (50 + 45 + 5, v/v/v) as the mobile phase with determination at 227 nm. The flow rate was 0.9 mL/min. The method was validated with respect to linearity, precision, accuracy, system suitability, and robustness. The responses were linear over the ranges of 1-80 and 5-200 microg/mL for alprazolam and sertraline, respectively. The recoveries of both drugs from a mixture of degradation products were in the range of 97-101%. The utility of the procedure was verified by its application to marketed formulations that were subjected to accelerated stability studies. The method distinctly separated the drugs and degradation products, even in actual samples. The products formed in marketed tablets were similar to those formed during stress studies.
本研究的目的是开发一种经过验证的、用于测定复方制剂中阿普唑仑和舍曲林的稳定性指示高效液相色谱法。按照国际协调会议规定的水解、氧化、光解和热应激条件对药物进行强制降解，从而验证该方法。以75 mM磷酸二氢钾缓冲液（pH 4.3）-乙腈-甲醇（50 + 45 + 5，v/v/v）作为流动相，在反相C18柱上成功地将药物与主要和次要降解产物分离，检测波长为227 nm。流速为0.9 mL/min。该方法在线性、精密度、准确度、系统适用性和稳健性方面得到了验证。阿普唑仑和舍曲林的响应分别在1 - 80和5 - 200 μg/mL范围内呈线性。两种药物从降解产物混合物中的回收率在97% - 101%范围内。通过将该方法应用于经过加速稳定性研究的市售制剂，验证了该方法的实用性。该方法即使在实际样品中也能清晰地分离药物和降解产物。市售片剂中形成的产物与应激研究中形成的产物相似。
