Bioequivalence study of bromhexine by liquid chromatography-electrospray ionization-mass spectrometry after oral administration of bromhexine hydrochloride tablets.

A simple, sensitive and specific liquid chromatography-electrospray ionization-mass spectrometry method was developed for the quantitative determination of bromhexine in human plasma. Sample preparation involved simple liquid-liquid extraction. Simvastatin was used as internal standard. The separation of the analyte, internal standard and possible endogenous compounds were accomplished on a Shim-pack ODS column (150 mm x 4.6 mm i.d., 5 microm) with methanol-water (98:2, v/v) as mobile phase. Detection was performed in positive selected ion monitoring (SIM) mode at m/z 264.1 (for bromhexine) and m/z 441.7 (for IS). The method was validated over the range of 0.5-60 ng/mL and the results were acceptable. The method could offer the advantages of shorter run time (5.5 min) and lower LLOQ (0.5 ng/mL) with a decreased plasma volume requirement (250 microL) and it had been successfully applied to a bioequivalence study in healthy Chinese volunteers after single oral administration of 16 mg bromhexine.