The Study And Application Of Analytical Method On Quality Control Of SPRC And Other Innovative Drugs

The research on quality control of drugs is an important part of drug pre-clinical studies. During the process of study on drug quality standards, an analytical method study of drug quality is needed to ensure accurate and reliable qualitative and quantitative analysis of drugs, and to guarantee the safety and reliability of drugs, and to guarantee the smooth progress of pre-clinical and clinical research, as well as the safety of post-marketing drugs. In vivo, the absorption, distribution, metabolism and excretion laws of drugs is reflected through pharmacokinetic parameters; therefore, pharmacokinetic study of drugs in vivo has important practical significance on quantitative study of drug in vivo distribution process.In the guidance of "Chinese Pharmacopoeia", "Chinese Veterinary Pharmacopoeia" and national relevant technical regulations on quality control of drugs, a study on analytical method of SPRC was conducted, and a comparation on columns, detectors in analytical method of SM934 was conducted, to determine the quantitative analytical method of SPRC and SM934. The analytical methods of providence and iodine in providence-high-complex-iodine oral liquid was studied, and a systemic study on quality standard was conducted, aim to establish the quality standard (draft) of povidone-high-complex-iodine oral liquid. A LC-MS-MS analytical method for determining the concentration of Berberine in Beagle dog plasma was developed, to establish the pharmacokinetic parameters of Berberine in Beagle dogs, which provided a theoretical basis for the distribution, metabolism and excretion laws of Berberine in vivo. The paper is divided into the following four parts:1、The study and application of the determination method on SPRC quality controlIn this chapter, the study on the determination method of SPRC quality control is based "Chinese Pharmacopoeia" and relevant technical specifications of the drug quality control. According to the property of SPRC, we selected non-aqueous titration and HPLC for its study and comparison. The impurity content of the drug exceeds the restriction of general chemical drugs, and the impurities are amino acids, which interfere with the determination of the main component, leaving the higher measurement result, so non-aqueous titration is not suitable in this situation for SPRC quantitative determination; However, the HPLC has relatively stronger specificity, and the measured results are accurate and reliable, which can be used for the determination of SPRC. The results show high levels of impurities in the drug, recommending optimizing the synthesis and purification process to reduce impurities.2、The study and application of the determination method on SM934 quality controlIn this chapter, the comparisons on columns and detectors of SM934 determination method are based "Chinese Pharmacopoeia" and relevant technical specifications of the drug quality control. Through the comparison for the columns of the same brand, the same packing, different lengths and different brands, the same packing, the same length, to determine the column used for the determination of SM934 was Dikma Diamonsil (?) C18 column (4.6 mm×150 mm,5μm). A comparison was made on the determination, related substances test and sensitivity of SM934 between HPLC UV detector and evaporative light scattering detector (ELSD). The results of related substances test measured by UV detector were significantly higher than the evaporative light scattering detector (ELSD), and the sensitivity of the UV detector is significantly higher, which lead to select UV detector used for the detection of SM934.In addition, the chapter also applied the established analytical method in the detection of SM934 and according to SM934 quality standards (draft), a full inspection on a batch of samples was conducted. The results are in line with requirements.3^ The study on quality standard of Povidone-high-complex-iodine oral liquidIn this chapter, the study on the determination method of povidone and iodine in povidone-high-complex-iodine oral liquid, the methods of identification and assay, and oral liquid quality standard is based "Chinese Pharmacopoeia" and relevant technical specifications of the drug quality control. According to the property of povidone, the method of the determination of povidone was established by HPLC. Potentiometric titration method and indicator titration method were respectively used to determine iodine, and ultimately indicator titration method is determined for quality control of iodine. The method of residual solvents determination was established. The results indicated that acetic acid and ethanol residues of povidone-high-complex-iodine oral liquid met the requirements of Chinese Veterinary Pharmacopoeia. Besides, the tests on pH, heave metal, arsenic salts, residue on ignition, microbial limit were conducted, and the results met all requirements.According to previous research, povidone-high-complex-iodine oral liquid quality standards (draft) and drafting instructions were drafted and formulated, which provide norms and basis for quality control of the povidone-high-complex-iodine oral liquid.4、Pharmacokinetic study of berberine in beagle dogsIn the chapter, pharmacokinetic study was focused on berberine administration alone and combined oryzanol administration in Beagle dogs, to evaluate oryzanol on absorption, distribution, metabolism and other effects of berberine in vivo. A LC-MS-MS analytical method was established for the determination of berberine in plasma, and the established LC-MS-MS method was applied to pharmacokinetic studies of berberine in Beagle dogs.In this chapter, the internal standard method for quantitative analysis of berberine in vivo was used. By the comparison of the concentration-time curves and other parameters as Tmax, Cmax, AUCO-t of berberine in the two group Beagles, it’s found that the two group test results had no significant correlation. The reasons may be due to the pre-experiment designed to take blood in a relatively short period, which led the third dog and the fourth dog not to reach peak concentration in test time. In addition, the dosing regimen and plasma processing method et al may exist some questions in certain degree, so the two-group results had no significant correslation. The series of issues ware to be modified in the official experiment, to achieve the desired results. The study (pre-experiment) ultimately did not achieve the desired results, but established LC-MS-MS analytical method and the experience of failure in the preliminary research can supply reliable, valuable data and meterials for the further pharmacokinetic studies of berberine.