Compatible Stability Study Of Cefathiamidine For Injection Combined With Four Infusions

Objective: To study the compatible stability of cefathiamidine for injection and four used clinically infusions with different pH value.Methods:1. Preparation of solutions1.1 Preparation of reference solution Dissolve 1g cefathiamidine in 10ml distilled water.1.2 Preparation of compatibility solutions According to the pH range of four infusions in China pharmacopoe- ia(CP),pH of each solutions were adjusted. 0.9% sodium chloride injections were adjusted to pH 4.50 and 6.99, 5% dextrose injections were adjusted to pH3.21 and 6.50, 10% dextrose injections were adjusted to pH 3.20 and 6.50,and 5%+0.9% dextrose and sodium chloride injections were adjusted to pH3.50 and 5.49. According to the clinical common dose confecting the compatibility of cefathiamidine and infusions above,and infusions unadjusted.The concentration of cefathiam- idine was 8mg/mL.2. Methodological studyThe method uses BDS- C18(250mm×4.6mm,5μm), phosphate buffer solution and acetonitrile (80:20) was mobile phase, at the detective wavelength of 254nm, with the flow rate of 1.0ml/min, at the temperature for 30℃, and the incoming sample amount for 1μL.2.1 Property testReference solution was diluted with mobile phase to 8mg/mL,and 1μL dilution was injected. Inject 1μL 0.9%NS,5%GS,10%GS and 5%+0.9%GNS,compare their chromatograms.2.2 Drawing of standard curve Dilute reference solution with mobile phase to 1,2,4,8and12 mg/mL,determine their peak area,and carry out regression analysis between peak area(Y)and concentration of cefathiamidine(C).2.3 Precision testInject 1μL reference dilution made in step 2.1 for 5 times,determine their peak area,and calculate relative standard deviation(RSD).3. Compatible stability study of cefathiamidine combined with four infusionsDetermine pH value of 0.9%NS,5%GS,10%GS,5%+0.9%GNS and their adjusted solutions. Dissolve 2g cefathiamidine in 250ml infusions above. pH value and external appearance changes (color and clarity) of the twelve compatibility solutions were determined at 0, 0.5, 1, 2, 3, 4, 5 and 6h.Inject 1μL of every solutions and determine their peak area.Results:1.The external appearance changes of compatibility solutions The twelve compatibility solutions are all yellowish and clear. There were no color changes ,no air bubble and deposition appearance under 24℃conditions in 6 hours.2. pH value changesThe pH value had nearly no changes in compatibility solutions of cefathiamidine and 5%GS(pH3.21),10% GS(pH3.20,pH3.72),5%GNS(pH3.50)in 6 hours. The pH value of compatibility solutions of cefathiamidine and 0.9%NS(pH 4.50,pH 5.62,pH6.99),5%GS(pH4.44,pH6.50),10% GS(pH6.50),5%GNS(pH5.49)had decreased slightly.3. The observation of content of cefathiamidine in compatibility solutions3.1 Property testUnder this chromatographic condition,the retention time of cefathiamidine is 5.88min,and the four infusions have no influence on it.3.2 The standard curveIn the range of 1～12mg/mL, peak area is linear relationship with the concentration of cefathiamidine, and the fitting equation is Y=1260682.4688C-2993.5313 (R=1.0000).3.3 Precision resultsThe RSD of Determination of cefathiamidine precision was 0.41%.3.4 The change of content of cefathiamidine in compatibility solutions The peak area of sample solutions decreased slightly with time- dependent, and decreasing degree was less than 4% within 6h.Conclusion After the compatibility of cefathiamidine and 0.9% sodium chloride injection, cefathiamidine and 5% dextrose injection, cefathiamidine and 10% dextrose injection and cefathiamidine and 5%+0.9% sodium chloride and dextrose injection with different pH value during 6 hours, at room temperature,they could kept an relative stability, can be used for clinic.