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

Objective:To establish an HPLC-MS method for the determination of azithromycin in serum and to e- valuate its pharmacokinetics parameters and bioavailability in healthy volunteers,nethods:A single dose of 500 me azithromycin was given to 20 healthy volunteers in a two-way cross-over design.The serum samples were collect ed at predetermind time before and after the administration,0.5 mL serum sample was alkalized with 0.1 me (0.5 mol·L~(-1)) sodium hydroxide solution and extracted with 4 mL methylene chloride.The serum concentration d azithromycin were determined by HPLC-MS method using Kromasil C_8(5μm,4.6 mm×250 mm)column,acete nitrile-water( containing 5 mmol·L~(-1) ammonium formate and 0.3% triethylamine) as mobile phase,with positivy ion SIM detection of azithromycin (M + H,m/z=749.5),using roxithromycin (M+H,m/z=837.5) as the interna standard.Results:The limit of detection for azithromycin was 2.5 ng·mL~(-1),and a linearity obtaining in the rang of 2.5-640 ng·mL~(-1) is good (r=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 after of 500 mg azithromycin tablets and capsules were as follows:t_(1/2)(h)35.7±3.9 and 35.5±3.3,T_(max)(h)2.30: 0.25 and 2.25±0.30,C_(max)(ng·mL~(-1))350.99±55.71and 344.23±60.60,AUC_(0～120)(ng·mL~(-1)·h)3951.9 ±497.12 and 3909.24±556.26,AUC_(0～∞)(ng·mL~(-1)·h)4303.66±529.61and 4254.33±589.98,respeetive ly.Conclusion:The established HPLC-MS method is highly sensitive and accurate,by which the results was dete mined is reliable.The pharmacokinetic parameter of azithromycin in our study show no significant difference be- tween tablets and capsules by statistic analyse,they are bioequivalence.