| Guanxinning injection, a traditional Chinese medicinal preparation refined from Radix Salvia miltiorrhiza and Rhizoma Ligusticum chuanxiong using water-extraction and alcohol-precipitation method, has been used to treat coronary heart disease and angina pectoris. It is recorded in the "Drug Standards of the Ministry of Health of the People’s Republic of China, the17th volume of Chinese patent medicine preparations". In this standards it only includes character identification,pH value,UV identification of Radix Salvia miltiorrhiza,TLC identification of Ferulic acid and HPLC determination of Protocatechuic aldehyde. This standards is not comprehensive and lack of specificity, which make it unable to control the drug quality effectively.In order to ensure the effectiveness, safety and technology rationality of Guanxinning injection, an exploratory research was carried out on the chemical constituents, quality control of effectiveness, safety control of harmful substances. The factors influencing product quality and relationship between refine technology and safety were also investigated. The details are as follows:1. Effective constituents and quality control method of Guanxinning injectionA method of fingerprint analysis by high performance liquid chromatography was developed, and13compounds were identified by comparing retention times and spectral data with that of authentic compounds. The fingerprint analysis suggested that sample’s quality from same manufacturers are similar, but there are obvious difference among the samples from different manufacturers. This results indicated that the preparation technology in same manufacturers is stable. The quantitative method of sodium danshensu, protocatechuic aldehyde, rosmarinic acid and salvianolic acid B from Radix salvia miltiorrhiza and ferulic acid from Rhizoma Ligusticum chuanxiong was established by HPLC and applied to evaluate the quality of Guanxinning injections from different manufactures. The big difference between different manufacturers was observed. A determination method of total phenolic with UV was also established.2. Safety related control method of Guanxinning injectionA UV quantitative method was used for determination of tannin in Guanxinning injection. It was found that the content of tannin have obvious difference among different manufacturers. An HPLC method was developed for the quantitative determination of5-HMF, and the contents in different Guanxinning injections were investigated. The results showed that samples from one manufacturer have higher5-HMF content than others. A quantitative method of high molecular mass impurities was also established by HPLC-RI. The all samples from one manufacturer detected high molecular mass impurities which was identified as Polysorbate80. Therefore, the quantitative method of Polysorbate80was developed by HPLC-ELSD.3.Investigation of factors influencing the quality of Guanxinning injectionFingerprint analysis of Radix Salvia miltiorrhiza and Rhizoma Ligusticum chuanxiong from different locations suggested that raw material is not the key factor affecting product quality. The different technological parameters which affect product quality such as alkali precipitation and acid precipitation were investigated. It was found that alkali precipitation can remove most of the tannin, and pH value in alkali precipitation and acid precipitation could affect the content of effective components. The sterilization test showed that the content of salvianolic acid B and ferulic acid decreased and5-HMF increased under high temperature. The refining processes utilized in different manufacturers were compared, and stricter test for abnormal toxicity and the blood coagulation were performed, meanwhile, the related components were determined. The results showed that refining process, composition and safety are closely related:①Abnormal toxicity and blood coagulation risk have obviously positive correlation with tannin content, and alkali precipitation decrease the content of tannin so as to improve drug safety.②Heat processing decrease the content of salvianolic acid B and ferulic acid and increase the content of5-HMF so as to increase the risk. The results made clear that reasonable technological parameters are deciding factors influencing the quality of products.The quality risk of Guanxinning Injection is mainly from the content reduction, increased impurity, safety reduction caused by improper refining technology, and lack of quality control of raw materials. Thus reasonable refining technology, perfect quality standard and controllable system can obviously reduce the quality risk. In order to control the quality of Guanxinning injection, we suggest that the fingerprint, multiple-component quantification, safety test, etc, should be added.and the preparation parameters should be comfirmed in the quality standard. |
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