Study On The Impurity Determination Of Piperazine And Hydrazine In Imatinib Mesylate

Methyl piperazine and hydrazine are key raw of imatinib mesylate(MIM)synthesis.Studying of the source,purge and removal is need to clarify.Establish enough sensitive analysis method for process research,impurity control and quality research are of great significance.Using solid-phase extraction(SPE)by GC determination for methylpiperazine of 4-[(4-methylpiperazin-1-yl)methyl]benzoic acid dihydrochloride(MIM60),and benzaldehyde derivatives by high performance liquid chromatography(HPLC)determination for hydrazine of Imatinib mesylate and N-(5-amino-2-methylphenyl)-4-(3-pyridyl)-2-pyrimidineamine(MIM50).The analysis method accuracy,sensitivity and precision was futher increasing.Results show that SPE-GC method of methyl piperazine cotent of MIM60,the solution was stable for 24 hours.The linearity coefficient of correlation was 1.0000 at the range 2.49-17.57 ?g/mL.The quantitation limit(QL)was 2.49 ?g/mL,the detection limit(DL)was 0.83 ?g/mL.The recovery was close to 100% at the range 2.50-15.00 ?g/mL.The relative standard deviation(RSD)for method precision was 1.3%.Stable and reliable method was accurate,effective quantitative content of methyl piperazine in MIM60,existing batches was lower than detection limit.Benzaldehyde derivatization-HPLC method of hydrazine content of MIM50 and MIM,the solution was stable for 24 hours.The linearity coefficient of correlation was 0.9999 at the range 0.023-0.180 ?g/mL of hydrazine content in MIM;the linearity coefficient of correlation was 1.0000 at the range 2.25-18.00 ?g/mL of hydrazine content in MIM50.The QL was 0.023 ?g/mL,the DL was 0.008 ?g/mL.The recovery was close to 100% at the range 0.023-0.128 ?g/mL of hydrazine content in MIM;the recovery was close to 100% at the range 2.25-12.75 ?g/mL of hydrazine content in MIM50.The RSD for precision was 1.5% of hydrazine content in MIM;The RSD for precision was 0.26% of hydrazine content in MIM50.Stable and reliable method was accurate,effective quantitative content of hydrazine in MIM50 and MIM,MIM50 batches was up to 0.02%,MIM batches was lower than detection limit.