Study On Quality Of Tacrolimus, Tacrolimus Capsules And Tacrolimus Ointment

Objective:To establish quality control measures of tacrolimus and its capsules, ointments.Methods:Carry out qualitative research of tacrolimus and its capsules, ointments,by means of modern and traditional analysis,such as HPLC,and so on, focusing on study of tautomerism and determination of drug substances,dissolution of its capsules,extraction of ointment.Shim-pack VP-ODS column(150mm×4.6mm,5μm) with temperature at 50℃was used with a mobile phase of isopropyl alcohol-acetonitrile-phosphoric acid solution(pH adjusted to 3.5)(35:2:63).The elution was performed at the flow rate of 1.0 ml/min.UV detection wavelength was 210nm.Results:For tacrolimus in aqueous solution,there is the phenomenon of tautomerism.With mobile phase as solvent,put at room temperature for about 6 hours of,tacrolimus and isomers ofⅠ,Ⅱachieve a balance in each variable;With 28% acetonitrile as solvent,70℃water bath for 10 minutes,and then at room temperature for about 2 hours,tacrolimus and isomersⅠ,Ⅱachieve a balance in each variable. When the injection volume was 50μl,the linear responses of tacrolimus range from 4.56～456μg/ml(r=1.0000,n=7).For capsules,carry out the dissolution test (Pharmacopoeia of The People's Republic of China,2005 Edition Aappendix XC,method 3),using 100ml of water as the dissolution medium,adjust the rotational speed of the paddle to 50rpm.Withdraw the solution after 5,10,20,30,45,60 minutes,respectively,determine the uniformity of dissolution,the result is consistent with the original product.With 28%acetonitrile as solvent,extracting ointments at 70℃water bath for 10 minutes,and then put in ice bath for 10 minutes,filtrating through membrane(0.45μm),the filtrate place at room temperature for 1.5 hours, injecting 100μl,the excipients have no interference on the results of assay of tacrolimus.The resolution between the peak of tacrolimus and the near impurity is good.The average recoveries of tacrolimus is 100.2%and RSD were 1.5%(n=9).Conclusion:The method is rapid,accurate,reproducible,and suitable for quality control.