Development and validation of RP-HPLC method for the determination of genotoxic alkyl benzenesulfonates in amlodipine besylate.

The present paper describes a simple isocratic reverse phase HPLC method for the determination of four genotoxic alkyl benzenesulfonates (ABSs) viz. methyl, ethyl, n-propyl and isopropyl benzenesulfonates (MBS, EBS, NPBS and IPBS) in amlodipine besylate (ADB). Good resolution between benzene sulfonic acid (BSA), MBS, EBS, NPBS, IPBS and ADB was achieved with Inertsil ODS 3V (150 mmx4.6 mm, 5 microm) column using a 65:35 (v/v) mixture of 1% triethyl amine, pH adjusted to 3.0 with orthophosphoric acid and acetonitrile as mobile phase. The flow rate was 1.0 ml/min and the elution was monitored at 220 nm. The factors involved in the method development are discussed. This method was validated as per International Conference on Harmonization (ICH) guidelines and is able to quantitate MBS, EBS, NPBS and IPBS at 21, 32, 35 and 28 ppm levels, respectively with respect to 5 mg/ml of ADB. The method is linear in range of 75-180 ppm of ABSs, which matches the range of 50-120% of estimated permitted level (150 ppm) of ABSs. ABSs were not present in the three studied pure and tablet batches of ADB.