Study On The Compatible Stability Of Azithromycin For Injection With Insulin

BackgroundAzithromycin is an Aza compound,belonging to the macrolide antibiotics,which can be used to treat community-acquired pneumonia and pelvic inflammation.Insulin is the only hormone in the body that lowers blood sugar.Azithromycin for injection is often combined with insulin in 5% glucose injection in clinical empirical medication to meet the treatment needs of diabetes and heart failure with limited salt.After reviewing the literatures,there is no research on the compatibility of the two and whether there is incompatibility is unknown.ObjectivesExplore the chromatographic separation conditions for the determination of insulin and azithromycin.Develop an accurate,sensitive HPLC method for the quantitative analysis.Study the compatible stability of insulin and azithromycin for injection.MethodsHPLC for the determination of insulin and azithromycin was performed,using Thermo SCIENTIFIC model Ulti Mate 3000 on a Ultimate XB-C18（5 μm,4.6×250 mm）column.The mobile phase was 0.2 mol/L sulfate buffer-acetonitrile（70: 30）,at the detective wavelength of 214 nm;the column temperature is 40℃ with the flow rate of 1.0 m L/min.According to these conditions,sampling the reference mixture,the peak area of insulin was recorded,the recovery rate,precision and linear relationshipof insulin were calculated,the durability of the method was investigated.The mobile phase was phosphatebuffer solution-acetonitrile（40:60）,at the detective wavelength of 210 nm;the column temperature is 35℃ with the flow rate of 1.0 m L/min.According to this chromatographic conditions,sampling the reference mixture,the peak area of azithromycin was recorded,the recovery rate,precision and linear relationship of azithromycin were calculated,the durability of the method was investigated.Determine p H values of the sample mixtures at room temperature and refrigerated respectively,observe external appearance and determine the content of insulin and azithromycin at different time,the stability of insulin and azithromycin under strong degradation was studied.ResultsRSD（%）of recovery rate,inter-day precision and within-day precision of insulin and azithromycin were all less than 2%.RSD（%）of the durability tests were less than 2%.There were no significant changes in p H values and external appearance of all mixtures at room temperature in 24 h.The contents of azithromycin were between 97% and 103%,the contents of insulin were between 96% and 103% compared with those prepared at 0 h undering the cold storage.The content of insulin was less than 105% at room temperature for 2 hours and the content changed by more than 110% with time.Undering all of the strong degradation conditions,insulin is unstable.Azithromycin is unstable only in the strong acid and the other strong degradation conditions do not affect the determination of azithromycin.ConclusionsThe HPLC methods established in this experiment for detecting insulin and azithromycin have strong specificity,high accuracy and good repeatability,which can meet the needs of in vitro study of compatible drugs.The content of insulin changes greatly at room temperature,so the mixture should be used within 2 hours,andit is better to use it immediately just when it is prepared.