ABSTRACT
OBJECTIVE: To determine two toxic impurities, namely bromoacetic acid and 4-aminobenzonitrile, in the intermediate of dabigatran etexilate by UHPLC-MS. METHODS: The separation was performed on a Shimadzu Shim-Pack GIS C18 column (2.1 mm×50 mm, 2 μm) with mobile phase consisting of 0.1% formic acid aqueous solution (A) and 0.1% formic acid methanol (B) by gradient elution at a flow rate of 0.4 mL·min-1. The detection was achieved by triple quadrupole mass spectrometry with rapid polarity switching using MRM mode. RESULTS: The calibration curves were linear in the ranges of 0.2-40 and 0.4-40 ng·mL-1 for bromoacetic acid and 4-aminobenzonitrile, respectively. The values of LOQ of bromoacetic acid and 4-aminobenzonitrile were 0.1 and 0.4 ng·mL-1, respectively. The recoveries of bromoacetic acid and 4-aminobenzonitrile were 100.9% and 99.6%, respectively. CONCLUSION: The method is accurate, rapid, sensitive, and reliable to determine the two toxic impurities bromoacetic acid and 4-aminobenzonitrile in the intermediate of dabigatran etexilate for quality control.