Thumma S, Zhang Shuang-Qing, Repka M A
Department of Pharmaceutics, School of Pharmacy, The University of Mississippi, University, MS 38677, USA.
Pharmazie. 2008 Aug;63(8):562-7.
A simple and rapid stability-indicating HPLC method was developed for determination of promethazine hydrochloride (PMZ) in hot-melt extruded (HME) films and sustained release tablets. Chromatographic separation was achieved on a 150 mm x 4.6 mm i.d., 3 microm particle size, C8 (2) column with acetonitrile-25mM phosphate buffer (pH 7.0), 50:50 (v/v) as mobile phase at a flow rate of 1 mL min(-1). Quantitation was achieved with UV detection at 249 nm based on peak area. The method was validated in terms of linearity, precision, accuracy, robustness specificity, limits of detection and quantitation according to ICH guidelines. Specificity was validated by subjecting the drug to acid, base, oxidative, reductive and dry heat degradations. None of the degradation products obtained by forced degradation interfered with the PMZ peak. The method was successfully applied for assessing the stability of the drug in the HME films and sustained release tablet formulations. In addition, uniformity of PMZ content in HME films was also determined using the method developed. Excipients present in either of the dosage forms analyzed did not interfere with the analysis indicating the specificity of the method. Due to its simplicity and accuracy, the method is suitable for application to various dosage forms.
建立了一种简单快速的稳定性指示高效液相色谱法，用于测定热熔挤出（HME）薄膜和缓释片中的盐酸异丙嗪（PMZ）。采用150 mm×4.6 mm内径、3μm粒径的C8（2）色谱柱，以乙腈-25 mM磷酸盐缓冲液（pH 7.0），50:50（v/v）作为流动相，流速为1 mL min-1进行色谱分离。基于峰面积，在249 nm处采用紫外检测进行定量。根据ICH指南，该方法在线性、精密度、准确度、稳健性、特异性、检测限和定量限方面进行了验证。通过对药物进行酸、碱、氧化、还原和干热降解来验证特异性。强制降解得到的降解产物均未干扰PMZ峰。该方法成功应用于评估药物在HME薄膜和缓释片制剂中的稳定性。此外，还使用所开发的方法测定了HME薄膜中PMZ含量的均匀性。所分析的任何一种剂型中存在的辅料均不干扰分析，表明该方法具有特异性。由于其简单性和准确性，该方法适用于各种剂型。
