Industrial Research Laboratory, Department of Pharmacy, Birla Institute of Technology and Science, Pilani, Pilani Campus, India.
Industrial Research Laboratory, Department of Pharmacy, Birla Institute of Technology and Science, Pilani, Pilani Campus, India; Birla Institute of Technology and Science, Pilani, Dubai Campus, United Arab Emirates.
Spectrochim Acta A Mol Biomol Spectrosc. 2021 Sep 5;258:119848. doi: 10.1016/j.saa.2021.119848. Epub 2021 Apr 17.
Temozolomide (TMZ) is a broad spectrum alkylating agent found effective in the treatment of glioblastoma multiforme, refractory anaplastic astrocytoma, and metastatic melanoma. The major drawback associated with TMZ is pH-dependent stability and short half-life. At physiological pH, it undergoes conversion to MTIC (methyltriazine imidazole carboxamide) and AIC (amino imidazole carboxamide), resulting in only 20-30% brain bioavailability. There is a need for an analytical method for the estimation of TMZ in stability samples and nanoformulations. In this research study, analytical methods were developed for the estimation of TMZ using two media pH 1.2 (0.1 N HCl) and pH 4.5 acetate buffer, which were validated for linearity, range, precision, accuracy, limit of detection, limit of quantification, and specificity as per ICH guidelines. The % RSD was found to be <2% indicating the reliability of the method. Further, the application of the developed methods was explored. The stability of TMZ in three pH conditions (1.2, 4.5, and 7.4) and the respective degradation rate kinetics was studied. Conversion of TMZ was found to follow first order kinetics with the conversion rate of 0.0011, 0.0011, and 0.0453 h in pH 1.2, 4.5, and 7.4 respectively. The developed methods accurately estimated the TMZ concentration in lipid nanoformulation (liposomes) indicated by ~100% recovery. Acetate buffer (pH 4.5) was found to be an appropriate dissolution media for TMZ loaded lipid nanoformulations. The developed methods were found to be suitable for routine analysis, for the determination of drug stability and estimation of temozolomide in lipid nanoformulations.
替莫唑胺（TMZ）是一种广谱烷化剂，在治疗多形性胶质母细胞瘤、难治性间变性星形细胞瘤和转移性黑色素瘤方面具有疗效。TMZ 的主要缺点是 pH 依赖性稳定性和半衰期短。在生理 pH 下，它会转化为 MTIC（甲基三嗪咪唑羧酰胺）和 AIC（氨基咪唑羧酰胺），导致脑内生物利用度仅为 20-30%。因此，需要一种分析方法来评估 TMZ 在稳定性样品和纳米制剂中的含量。在这项研究中，开发了两种介质 pH 1.2（0.1 N HCl）和 pH 4.5 醋酸缓冲液中用于 TMZ 估计的分析方法，并根据 ICH 指南对线性、范围、精密度、准确度、检测限、定量限和专属性进行了验证。发现 %RSD 小于 2%，表明方法的可靠性。此外，还探索了所开发方法的应用。研究了 TMZ 在三种 pH 条件（1.2、4.5 和 7.4）下的稳定性及其各自的降解速率动力学。发现 TMZ 的转化遵循一级动力学，在 pH 1.2、4.5 和 7.4 下的转化率分别为 0.0011、0.0011 和 0.0453 h。开发的方法能够准确估计脂质纳米制剂（脂质体）中 TMZ 的浓度，回收率约为 100%。发现醋酸缓冲液（pH 4.5）是 TMZ 负载脂质纳米制剂的合适溶解介质。所开发的方法适用于常规分析，用于测定药物稳定性和估计脂质纳米制剂中的替莫唑胺。
