Abstract��
OBJECTIVE To establish a LC-MS/MS method for the determination of clarithromycin in human plasma and to study pharmacokinetics and relative bioavailability of clarithromycin sustained-release capsule and clarithromycin sustained-release tablet in market. METHODS The tested drug and internal standard roxithromycin were extracted from plasma samples by ether-dichloromethane(3��2) and chromatgraphed on a C18 column. The mobile phase consisted of methanol-water-formic acid (80��20��0.05).Detection was performed on a triple quadrupole tandem mass spectrometer via electrospray ionization source(ESI) in the positive mode. RESULTS The linear calibration curves were obtained in the concentration range of 10.0��4 000 ��g��L-1. The intra-and inter-run precisions were lower than 15% in terms of relative standard deviation. Pharmacokinetic parameters of the two products after the administration of 0.5 g clarithromycin to 18 volunteers were as follows:tmax(5.36��1.14) and (5.25��0.88) h,��max(1 218��433) and (1 333��370)��g��L-1,t1/2(4.59��1.67) and (4.24��2.10)h,AUC0-t(8 239��1 553) and (8 467��1 364)��g��h��L-1,AUC0-��(8 662��1 829) and (8 795��1 331)��g��h��L-1,CL(60.9��15.1) and (58.9��11.3)L��h-1,Vd(382��103) and (366��224)L,for a single dose,respectively;tmax(5.31��1.11) and (5.28��0.96) h,��ssmax (1 387��396) and (1 488��401) ��g��L-1,��ssmin(64.6��26.8) and (70.1��30.0) ��g��L-1,��av(399 ��99.2) and (410��107) ��g��L-1,AUCss(9 585��2 382) and (9 830��2 578) ��g��h��L-1,DF(3.32��0.62) and (3.49��0.66) for multiple doses,respectively. The relative bioavailability of the test drug for single dose and multiple doses were(98.2��16.3)% and (99.5��19.0)%. CONCLUSION This method is fast,sensitive and accurary.There is no difference between the test and the reference drugs of clarithromycin in the relative bioavailability (P>0.05).
2009, Vol. 44 
