Study On The Methods Of Online Process Monitoring And Quality Control Of Qingkailing Injection

Objective: Online process monitoring and control of pharmaceutical manufacturing processes are systems for design, analysis, and control of manufacturing processes, based on timely measurements of critical quality and performance attributes of raw and in-process materials and products, to assure stability and homogeneity of products at the completion of manufacturing. Implementing online quality control of the medicines production is the trend of traditional Chinese medicines standard. In this study, Qingkailing injection was selected as an example to develop rapid quality evaluation methods. The key steps in the production process were confirmed. The quick quality appraisal methods of the intermediates and the preparation were established. All these provided the base of methodology of online quality control of qingkailing injection.Methods: The formula of Qingkailing injection is composed of cholic acid, hyodeoxycholic acid, Concha Margaritifera, Radix Isatidis, Cornu Bubali, baicalin, Fructus Gardeniae, and Flos Lonicerae Japonicae. The correlation analysis between different measuring and testing techniques was used to quickly determine the marker and active ingredients; Comparison of similarity degree of UV spectra was used to evaluate the integerity and homogeneity.Ⅰ. Three kinds of methods of determining the content of total nitrogen (TN) of the hydrolyzed solution and the aqueous solution of Radix Isatidis extraction (ASRIE) were compared.①Improved ninhydrin colorimetry. The reaction conditions includes adjusting the pH of the prime sample to 8, adding 2% aqueous solution of ninhydrin 1mL and pH=8 buffer 0.5mL, and heating the samples in the boiling water for six minutes. The best correlating wavelength was selected to bulid the model for predicting the content of TN.②Total organic carbon / Total nitrogen determination (TOC/TN). Analyzer and its option unit TNM-1(Total Nitrogen Measurement) were used to measure the TN content in the Qingkailing injection and its intermediate products. High purity air was used as carrier gas at a flow rate of 150mL?min-1. The temperature of combustion tube was 720℃. Chemical luminescence detector was selected.③NIR spectrometry. The conditions of establishing the model for predicting the TN content of the hydrolyzed solution: Original spectrum was selected. Stepwise multiple linear regression (SMLR) was used to data process. The selected wavenumbers were 6608.86 cm-1 and 7170.04 cm-1; the conditions of establishing the model for predicting the TN content of ASRIE: Original spectrum was selected, and SMLR was used as a data processing method.