An Orthogonal Approach for Method development, Validation and Trace Level Quantification of 2,5-Diamino-4,6-dichloro Pyrimidine Impurity in Abacavir Sulfate by LC-MS/MS and GC-MS

摘要

The trace level quantification of 2,5-diamino-4,6-dichloro pyrimidine (DADCP) present in abacavir sulfate by LC-MS/MS and GC-MS has been proposed. LC-MS/MS method was established for 2.5 ppm with respect to test concentration (10 mg/mL), LOQ and LOD were established as 1.3 and 0.4 ppm, respectively. Linearity, method precision, accuracy at LOQ, 100 %, 150 %, solution, mobile phase stability and robustness parameters were studied against the ICH Q2(R1) guideline. Similarly, the GC-MS method was established for 2.5 ppm of 2,5-diamino-4,6-dichloro pyrimidine with respect to test concentration (50 mg/mL), LOQ and LOD were established as 1.1 and 0.4 ppm, respectively. Linearity, method precision, accuracy at LOQ, 100 %, 150 %, solution stability and robustness parameters were studied against the ICH Q2 (Rl). No analytical method was found in trace level quantification of 2,5-diamino-4,6-dichloro pyrimidine in abacavir sulfate. The orthogonal method of LC-MS/MS and GC-MS was well robust and can be used for determination of trace level of 2,5-diamino-4,6-dichloro pyrimidine in different pharmaceutical compounds.