Verification Of Structure And Study On Quality Control In Oxaliplatin

Oxaliplatin,oxalic acid (1R,2R-cyclohexanediamine)platinum(â…¡),is the firstclinically available diamino-cyclohexane platinum coordination complex.The drugis non-cross-resistant with cisplatin or carboplatin and is one of the few active drugsagainst human colorectal cancer.In this study, the structure of synthetic compound was conformed by UV, IR,EIS-MS,NMR along with element analysis,thermal analysis and X-raydiffraction(XRD).The results showed that the structure of the compound wasidentical with oxaliplatin, residue on ignition method was developed for thedetermination of content of purified oxaliplatin,the average contents was99.68%(n=3).Till now pharmacopoeias including USP, Chp and BP have not described thequality standard of Oxaliplatin.Quality control method of Oxaliplatin andOxaliplatin for Injection were studied comprehensively in this thesis.RP-HPLC wasdeveloped for the assay and durg-related impurities in raw drugs and injections.Luna C₁₈ column (200×4.6 mm i.d 5μm) with UV detection at 250 nm, and themobile phase consisted of methyl alcohol-water (5:95)were used. The calibrationcurve was linear (r=0.9999) within the range of 5～600μg·ml^-1 for Oxaliplatin, thedetection limit was 3ng (S/N=3).The between-day precision RSD was 0.15%(n= 5)for raw drugs and 0.29%(n=5) for injections, the repeatability RSD was 0.17%(n=6) for raw drugs and 0.30% for injections, and the average recovery was from100.1% to 102.4% for three different levels of the amount of injections,RSD wasfrom 0.15% to 0.74%; the limit of drug-related impurities was 1.0% for raw drugsand injections.HPLC-chiral chromatographic column was developed for levoisomerof Oxaliplatin (CHIRALCELOC-H, the column contains a carbamate cellulosederivative coated silica gel as the packing material of Daicel chemical industrycompany of Japan,250mm×4.6mm,5μm),The mobile phase wasmethanol-ethanol(70:30);The detector was at 250nm. the limit of levoisomer ofOxaliplatin was 0.5%. It was also examed about character, content and drug-relatedimpurities during 6 months' acceleration test under 60℃and 12 months' storageunder room temperature based on quality standard already established. Stability trialshows that Oxaliplatin has its degradation in the situation of high temperature,illumination,high humidity, and has slightly hygroscopicity in high humidity,therefore it should be kept out of sunshine and closed tightly.This method wassimple, accurate and suitable for the quality control for Oxaliplatin and Oxaliplatinfor Injection.