The Exploratory Research Of Paclitaxel Injection In Quality Control And Clinical Safety Application

Objective:Establish a more comprehensive quality evaluation system of paclitaxel injection by examining the influence of p H, moisture content and organic residual solvent on quality of paclitaxel injection; Evaluate the safety of paclitaxel infusion in clinical by analyzing the dissolution conditions of diethyl hexyl phthalate(DEHP) of the infusion apparatus in paclitaxel injection; Provide guidance for the safe use of paclitaxel injection in clinical by investigating the compatibility stability of paclitaxel injection with three kinds of clinical injection: 0.9% sodium chloride injection, 5% glucose injection and glucose and sodium chloride injection.Methods:Using the high performance liquid chromatography(HPLC) in 2010 version of“China pharmacopoeia” about determination of related substances in paclitaxel injection,the main impurity contents in the paclitaxel injection under different conditions, such as p H in 3.6 and 6.4, moisture content in 0.3%, 2.8%, 4.5%, 10.0%(under different temperature and light conditions placed at different times), and blend with above-mentioned three kinds of clinical injection, were quantified and compared, respectively. Employing headspace gas chromatography, we determine the contents of organic residual solvents in paclitaxel raw materials and preparations; Applying HPLC, we detect and compare the dissolubility of DEHP in ordinary polyvinyl chloride(PVC) and ultra low density PVC infusion apparatus.Results:The contents of major impurities in paclitaxel injection have significant differences at different p H and moisture content; The seven kinds of organic residues and their detection limits in the paclitaxel raw materials and its injection are methanol(0.075% g/ml),acetonitrile(0.01% g/ml), hexane(0.007% g/ml), cyclohexane(0.097% g/ml), ethyl acetate(0.125% g/ml), pyridine(0.005% g/ml), toluene(0.02% g/ml). Several residual solvents of paclitaxel in raw materials and formulations in different manufacturers were detected, buttheir contents did not exceed the limits; DEHP was undetected in liquid collection from the ultra-low-density PVC infusion apparatus, however, DEHP could be detected by using normal PVC infusion apparatus and its content was 0.0389 g; The contents of main impurities in the mixed solution of paclitaxel injection and three kinds of injection were no obvious changes, but dissolve of paclitaxel injection was relatively slow.Conclusion:In this study, the quality evaluation of paclitaxel injection and the investigated results of common infusion apparatus and three kinds of injections in clinical provide a scientific basis and experimental evidence for the safe use of paclitaxel injection in clinical.