Study On The Quality Standard And Stability Of Class1.1New Antiarrhythmic Drug PDD1

Pseudoginsengenin DD1(PDD1),(20S,24S)-dammar-20,24-epoxy-3β,12β,25-triol, issemi-synthesized with protopanaxdiol as start material. Molecular formula: C30H52O4,molecular weight:476.4. It was indicated that the compound showed a good anti-arrhythmiceffect and little toxicity according to the pharmacology and toxicology studies. Therefore,there will be a broad market prospect if PDD1is developed as a class1.1innovativeantiarrhythmic drug.According to the guiding principle of chemical drug class1.1and the ChinesePharmacopoeia (2010edition), the PDD1(drug substance) and its pills (product) pre-clinicalpharmaceutical research were performed by using three batch scale-up samples. In this paper,the quality standards drafts of drug substance and product have been established. Meanwhile,the stability of drug substance and product also has been studied, including the influence factortest, accelerated test and long-term test.Research of the quality standards:(1) We inspected some items of PDD1bulk drugs, suchas: external appearance, solubility, melting point, identity, clarity of solution, loss on drying,residue on ignition, heavy metal, chlorine compounds, arsenide, related substances and contentdetermination.(2) The items of PDD1pills being inspected were as follows: externalappearance, identity, content uniformity, weight difference, dissolution time, microbial limit,residue on ignition, heavy metals, arsenide, related substances and content determination.(3)The quality standards of PDD1bulk drugs have been established.(4) We also established thequality standards of PDD1pills.In this paper, the HPLC-ELSD was firstly used to establish drug substance’s andproduct’s content determination method. As for PDD1bulk drugs, it is requested that thecontent of C30H52O4couldn’t less than98.0%calculated on dry product. As for PDD1pills, itis requested that PDD1(C30H52O4) in the pills must in the range of90%to110%of labeled amount. At the same time, we inspected its specificity, linearity, stability, precision,reproducibility and recovery rate. The results showed that the method was simple, accurate,sensitive and reproducible. The linear was perfect in the range of0.6-6.0μg. This fullyvalidated method could be applied to control the quality of drug substance and product.In the examination of related substances, it is the first time to establish an HPLC-ELSDmethod for related substances’ determination of PDD1drug substance and product. Themethod of principal components self-control without the correction factor had been used in theprocess of determination. The specificity, linearity, stability, precision, reproducibility andrecovery rate were also studied, and the results showed that the method was simple, rapid andsensitive; the results were accurate and reproducible.Stability testing: In order to provide the scientific data for drug production, packaging,storage, transportation conditions and expiry date, the changes of drug substance and productwith temperature, humidity and light were investigated in this paper. Based on the drugstability testing guidelines and the Chinese Pharmacopoeia (2010edition), three batch scale-upsamples in the same packaging as marketed one. Test the bulk drugs mainly from the externalappearance, melting point, clarity of solution, loss on drying, related substances and contentdetermination. Test the pills mainly from the external appearance, identity, weight difference,dissolution time, microbial limit, related substances and content determination.(1) Influencefactor testing: The sample of0,5,10days were detected under high temperature, humidity andlight. The results showed that drug substance and product were stable without any newdegradation product.(2) Accelerated testing: The drug substance and product were placed inthe condition of40℃±2℃and75%±5%(RH) for6months. The samples on the end of0,1,2,3,6months were detected. The results showed that, under extraordinary conditions,PDD1bulk drugs and pills were stable.(3) Long-term testing: The drug substance and productwere placed in the condition of25℃±2℃、RH60％±10％for12months. The samples onthe end of0、3、6、9、12months were detected. The results also showed that PDD1and pillswere stable.In a word, this study will provide a scientific method for PDD1drug substance’s andproduct’s quality control with the establishment of quality standards. And then, byinvestigating PDD1’s and pills’ change with temperature, humidity and light, a solid theoretical basis will be provided for the production, packaging, storage, transportationconditions and expiry date.