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.
Zhang
Wen
W
Department of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing 210009, PR China.
Feng
Fang
F
Wang
Ya
Y
D000284:Administration, Oral; D019540:Area Under Curve; D001964:Bromhexine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D002138:Calibration; D002853:Chromatography, Liquid / Q000379:methods*; D018592:Cross-Over Studies; D004355:Drug Stability; D005100:Expectorants / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005615:Freezing; D006207:Half-Life; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D011786:Quality Control; D012015:Reference Standards; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D013607:Tablets; D013810:Therapeutic Equivalency
D005100:Expectorants; D013607:Tablets; D001964:Bromhexine