Hetero Drugs Ltd. (R&D), Plot No. B. 80 & 81, APIE, Balanagar, Hyderabad 500018, India.
Hetero Drugs Ltd. (R&D), Plot No. B. 80 & 81, APIE, Balanagar, Hyderabad 500018, India.
J Pharm Biomed Anal. 2014 Feb;89:276-81. doi: 10.1016/j.jpba.2013.11.013. Epub 2013 Nov 19.
Six sensitive derivatization methods for the determination of genotoxic impurities in selected drug substances were developed using hyphenated techniques. Some of the raw materials, reagents and reaction intermediates of the selected drug substances were identified as genotoxic impurities through DEREK software for windows. The genotoxic impurities which are amenable for derivatization were selected as substrates. Derivatizing agents were selected based on the functional groups of the genotoxic impurities. The chemistry involved in the derivatization was explained with suitable mechanisms. An appropriate hyphenated technique viz. LC-MS and GC-MS was opted based on the sensitivity and aromaticity of the derivatized genotoxic impurities. All the methods were validated as per International Conference on Harmonization guidelines. Correlation coefficient values were found about 0.99. The obtained % R.S.D values from replicate injections in the range of 2.3-4.8 and % recoveries of the added impurities in the range of 83.7-101.7 ensured the precision and accuracy, respectively.
六种灵敏的衍生化方法被开发出来，用于通过联用技术测定选定药物中的遗传毒性杂质。通过 DEREK 软件，一些选定药物的原料、试剂和反应中间体被鉴定为遗传毒性杂质。选择可衍生化的遗传毒性杂质作为底物。根据遗传毒性杂质的官能团选择衍生化试剂。用合适的机制解释了衍生化过程中的化学变化。根据衍生化后遗传毒性杂质的灵敏度和芳香性，选择了合适的联用技术，即 LC-MS 和 GC-MS。所有方法均按照国际人用药品注册技术协调会的指导原则进行验证。相关系数值约为 0.99。在 2.3-4.8 的范围内，从重复进样中获得的%R.S.D 值和添加杂质的%回收率在 83.7-101.7 的范围内，分别确保了精密度和准确度。
