Determination of Potential Genotoxic Impurities (Orthophenylene Diamine Dihydrochloride), 4'-Bromomethyl-2-Cyanobiphenyl, 4'(Dibromomethyl)[1,1'-Biphenyl]-2-Carbonitrile in Telmisartan by ESI-MS/MS.

A sensitive, simple, rapid and robust LC-MS/MS method was developed for the determination of potential genotoxic impurities OPDA HCl (orthophenylene diamine dihydrochloride), bromo OTBN (4'-bromomethyl-2-cyanobiphenyl), dibromo (4'(dibromomethyl)[1,1'-biphenyl]-2-carbonitrile) in Telmisartan by using ESI-MS/MS Technic; the study was performed with gradient elution (time/% mobile phase B: 0/10, 3/10, 30/80, 35/80, 36/10, 40/10). The mobile phase consisted of a mixture of formic acid, methanol and acetonitrile. The buffer was degassed before running at a flow rate of 1.0 mL/min. The column temperature was at 40°C. The 20 μL volume of sample was injected per run and peaks were detected using DAD detector. The LC-ESI/MS/MS studies were carried out on Ultivo Triple Quadrupole LC/MS/MS (Agilent, USA) G6470A mass spectrometer, ion source voltage 3500 V, de clustering potential 40 V, entrance potential 10 V, with the nebulizer gas as nitrogen at 45 psi. The LC part consisted of Agilent 1260 series HPLC system with binary gradient pump with a degasser and an auto sampler. Inert sustain AQ-C18, 250 × 4.6 mm, 5-μm particle size was used for chromatographic separation. Developed method is validated as per ICH guidelines and found to be linear, accurate, specific, selective, precise and robust. Test solution was found to be stable up to 48 h. This method can be successfully applied for the determination of genotoxic impurities in Telmisarta for routine analysis and stability assessment.