The Test Of The Human Bioequivalence Of Oxacilin Sodium Capsules

At present,compared with other developed countries in the field of new drug development,China has many insufficiencies, because we change medicine just by changing the medication dosage form or adding some accessories, therefore many drugs are generic drugs.when generic medicine comes into the market,we just check whether its drug properties are same with the copy drug.Therefor,the bioequivalence study became very important. High performance liquid chromatography- tandem mass spectrometry with strong specificity and high sensitivity advantages is more and more widely used in bioequivalence test.Objectives:Oxacillin belongs to semisynthetic Isoxazoles,which has a property of resistance of acid and staphylococcal penicillinase.Oxacillin has a good effective antibacterial activity to staphylococcus of producing penicillin and is effective to staphylococcus aureus which can make enzyme,while it is less effective to antibacterial activity than penicillin G on all kinds of streptococcus and staphylococcus that do not produce penicillinase.This product has a good curative effect, good resistance and high safety, which is the ideal of antimicrobial agents.This test is used to study the human bioequivalence trial of Oxacillin Sodium Capsules producted by North China Pharmaceutical Co.,LTD, Oxacillin Sodium Capsules producted(Commodity name,Qi Fei) by Sichuan pharmaceutical co., LTD as a reference preparation.Methods:1 This test describe a method that measure drug concentration of Oxacillin Sodium Capsules in human blood with HPLC-MS/MS.After protein deposition treatment of the biological sample,we use the exclusive and sensitive LC-MS/MS to measure,adopting internal standard method to quantitate according to the ratio of the peak area and internal standard peak area.In this method, the dosage of plasma is 50 mL,and the minimum quantitative concentration is 0.1μg·m L-1.2 According to the standard of selected subjects and exclusion criteria,in experiment,we chose 20 subjects from 28 male volunteers into the experiment,including one subject exiting the experiment because of his suspicious positive penicillin skin test and one candidates chosen.All of the 20 subjects complete the whole process of the test and we analyze the whole data. With an open, randomized and double cross experiment design to proceed the bioequivalence test of this item,according to the experiment designed, 20 male subjects take orally a single dose of 1000 mg of reference preparation and tested preparation,we use HPLC-MS method to measure the concentration of Oxacillin Sodium Capsules in human blood,and finally we use DAS software to fitting calculate the pharmacokinetic parameters and evaluate bioequivalence.Results:The coming time of the peak of tested preparation and reference preparation(tmax) is 0.63±0.14 and 0.72±0.26 h respectively;The peak concentration(Cmax) is 17.0±2.77 and 15.5±3.46μg·m L-1 respectively;The AUC0-6h is 22.52±4.38 and 22.54±5.79μg·m L-1·h respectively; The AUC0-∞ is 23.06±4.56 and 22.91±5.82μg·m L-1·h;We find that the there was no significant difference between tested preparation and reference preparation after nonparametric rank sum test is used to tmax;And there are no difference between tested preparation and reference preparation after the analysis of variance of Cmax, AUC0-6h and AUC0-∞ been logarithmic transformation. Two one-side t test shows that 95% confidence interval of Cmax of tested preparation is found in reference preparation ranging from 75% to 133%,and 90% confidence interval of AUC of tested preparation is found in reference preparation ranging from 80% to 125%;With the AUC0-6h of Oxacillin calculated,the relative bioavailability of tested preparation Oxacillin is(102.8±19.3)%.Conclusions:1 This experiment establishes the plasma sample processing method and the method of measuring drug concentration of Oxacillin Sodium Capsules in human blood in HPLC-MS/MS.In addition to the simple sample processing,this method is exclusive, accurate and high sensitivity,and, hence it is suitable for clinical pharmacokinetic study and meets the analysis of Oxacillin Sodium sample.2 Through the double cross experiment of 20 healthy male subjects single taking the Oxacillin Sodium Capsules(A) developed by North China Pharmaceutical Co., LTDand the reference preparation of Oxacillin Sodium Capsules(R),we prove that the tested preparation of Oxacillin Sodium Capsules has the same bioequivalence with commercially available reference preparation,and the respective bioavailability of the tested preparation and the reference preparation of Oxacillin Sodium Capsules is(102.8 + 19.3) %.