Study of pharmacokinetics and relative bioavailability of azithromycin tablets and capsules by HPLC-MS method

To establish an HPLC-MS method for the determination of azithromycin in serum and to evaluate its pharmacokinetics parameters and bioavailability in healthy volunteers.MethodsA single dose of 500 mg azithromycin was given to 20 healthy volunteers in a two-way cross-over design.The serum samples were collected at predetermind time before and after the administration,0.5 mL serum sample was alkalized with 0.1 mL(0.5 mol·L-1)sodium hydroxide solution and extracted with 4 mL methylene chloride.The serum concentration of azithromycin were determined by HPLC-MS method using Kromasil C8(5 μm4.6 mm×250 mm)column,acetonitrile-water(containing 5 mmol·L-1ammonium formate and 0.3%triethylamine )as mobile phase,with positive ion SIM detection of azithromycin(M+H,m/z=749.5),using roxithromycin(M+H,m/z=837.5)as the internal standard.ResultsThe limit of detection for azithromycin was 2.5 ng·mL-1,and a linearity obtaining in the range of 2.5-640 ng·mL-1 is goodr=0.9998)with HPLC-MS method.The relative standard deviations of within-day and between-day determination were less than 6%.The main pharmacokinetic parameters after a single dose of 500 mg azithromycin tablets and capsules were as follows:t1/2(h)35.7±3.9 and 35.5 ± 3.3,Tmax(h)2.30±0.25 and 2.25±0.30,Cmax (ng·mL-1)350.99±55.71and 344.23±60.60AUC0120(ng·mL-1·h)3951.90 ±497.12 and 3909.24±556.26AUC0∞(ng·mL-1·h)4303.66±529.61and 4254.33±589.98respectively.ConclusionThe established HPLC-MS method is highly sensitive and accurate,by which the results was determined is reliable.The pharmacokinetic parameter of azithromycin in our study show no significant difference between tablets and capsules by statistic analyse,they are bioequivalence.

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