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??OBJECTIVE To discuss the problem of instrumental test method of clarity and degree of opalescence of liquids in the general notice 0902 of China Pharmacopeia(Ch.P)2015, find out the causes and offer solutions. METHODS The test methods of clarity in Ch.P 2015 and European Pharmacopeia (EP) 8.0 were compared, including instrumental types, applicability, sample requirements, and result evaluation. RESULTS The primary opalescent suspension for the instrumental method is the same as the visual method, using the absorbance (A=0.12-0.15) at 550 nm to control the opalescence. Because the resolving power of the instrumental method is far higher than the visual method, the limit becomes interval distribution instead of simple point. The opalescent value (NTU) of the upper limit (A=0.15) is about 1.35 times of the lower limit (A=0.12).When the NTU value of the test liquid is in this interval, the result evaluation will be hard.CONCLUSION The preparation of the primary opalescent suspension in Ch.P 2015 is different from EP8.0. For this reason, the limit set by Ch.P 2015 is actually stricter than that of EP8.0. The opalescent value of the standard solution used by Ch.P 2015 is about 75% of that used by EP8.0.     

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??OBJECTIVE To establish an HPLC method for rapid screening and simultaneous determination of 10 preservatives in eye drops and assess their antimicrobial effectiveness. METHODS A Waters XBridge C₁₈ column (4.6 mm??150 mm,5 ??m) was used, and the mobile phase was 0.1% phosphoric acid-methanol-THF eluted in gradient mode at a flow rate of 1.0 mL??min^-1. The detection wavelength was set at 214 nm. The antimicrobial effectiveness of the preservatives was assessed according to Ch. P 2015. RESULTS The calibration curves were linear in the range of the corresponding test concentrations (r=0.999 3-1.000 0). The recoveries were between 96.1%-101.8%. One of the eye drops products did not meet the requirement of Ch. P 2015. CONCLUSION The established method is rapid and inexpensive. And it ensures excellent simplicity, sensitivity, specificity, and reproducibility and can be used for rapid screening and determination of the contents of preservatives in eye drops. The amount of preservatives should be established during the R&D period or determined according to the RESULTS of antimicrobial effectiveness test rather than using empirical values.     

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??OBJECTIVE To evaluate the equivalence among three different methods for drug melting point determination:??method A1 by glass liquid thermometer, ??method A2 by digital display,and ?? method B by instrumental method. METHODS Five chemical reference substances with different melting points were selected as the target drugs, and different brands of melting point apparatus were used to determine melting point. The apparatus used by method A consists of a glass container for a liquid bath and fitted with a suitable means of heating.The obtained results of the melting point by method A1, A2 and B were evaluated by equivalence testing referring to the data of Proficiency Testing Scheme for the melting point determination of chemical drugs organized by NIFDC in 2015 and 2016. RESULTS Method A1, A2 and B were equivalent,and no significant difference were observed for the melting point values determined by the three methods. CONCLUSION There is no significant difference between the melting point determination method A and method B in the Chinese Pharmacopoeia(Ch.P), and the obtained melting point values are equivalent either by glass liquid thermometer or digital display while using method A. This experiment provides scientific data support for potential adoption of digital display in melting point apparatus by Ch.P.     

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??OBJECTIVE To develop methods for quality control of humanized monoclonal antiboy (McAb) against vascular endothelial growth factor (VEGF).METHODS The purity of humanized anti-VEGF McAb was determined by reduced and non-reduced sodium dodecyl sulfate capillary electrophoresis (CE-SDS), while the contents of monomer and polymer were determined by size-exclusive high performance liqud chromatography (SE-HPLC) at the concentration of 0.5 and 25.0 mg??mL^-1, respectively. Isoelectric point was determined by isoelectric focusing capillary electrophoresis (cIEF), and the content of charge isomers was controled by cation exchange HPLC(CEX-HPLC). For identity, Lys-C digested peptide map was analyzed by RP-HPLC and LC-MS. The biological potency of anti-VEGF McAb was determined with a human umbilical vein endothelial cells (HUVEC) proliferation inhibitory test. And other quality indexes required by the Ch.P and other relevant requirements were also investigated. RESULTS The purities of drug substance (DS) and products (DP) determined by reduced CE-SDS were (97.77??0.25)% and (97.43??0.57)%, respectively. The purities of DS and DP determined by non-reduced CE-SDS were (98.97??0.15)% and (98.73??0.06)%, respectively. In the SE-HPLC analysis, when the concentration of McAb was 0.5 mg??mL^-1, the monomer contents of DS and DP were (98.07??0.55)% and (98.20??0.52)%, while the contents of polymer in DS and DP were (2.00??0.53)% and (1.93??0.55)% at the concentration of 25.0 mg??mL^-1. In the CEX-HPLC analysis, the contents of the acidic, main, and basic components of DS and DP were (18.33??0.64)% and (18.60??0.44)%, (69.03??0.80)% and (69.20??0.44)%, (12.70??1.37)% and (12.20??0.87)%, respectively. In the cIEF and LC-MS tests, the DS and DP showed consistency in isoelectric point and peptide map with reference materials. The other quality indexes all met the requirements in Ch.P and other relevant requirements. CONCLUSION The mthods for quality control of McAb against VEGF is successfully developed, which can be used for the routine quality control of the product.     

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??OBJECTIVE To compare two biological standardization calculation methods for evaluating the anticoagulation activity of different leeches in the same measure. METHODS Heparin was used as the reference substance. The APTT values of W. pigra, H. nipponica and P. manillensis were used as the anticoagulant activity evaluation potency. The slope ratio model of European Pharmacopoeia 7.0 and the parallel reaction model of Ch.P 2015 were used to calculate the activity and the results were compared. RESULTS The logarithm dose response curves of three kinds of leeches displayed linear relationship. Both of biological standardization statistical methods could be used for the calculation. The slope ratio model complete randomized design(0,3,3) of European Pharmacopoeia 7.0 was suitable to calculate the activity potency of different leeches, but the parallel reaction model of Chinese Pharmacopoeia 2015 was only suitable for P. manillensis. CONCLUSION Taking the anticoagulation potency of heparin sodium as the reference, the slope ratio model complete randomized design(0,3,3) of European Pharmacopoeia 7.0 can be used as a standard method to evaluate the anticoagulation activity of different leeches.     

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??As one kind of lipid excipients, triacylglycerols (TAGs) are being more and more widely used in pharmaceutics with the development of advanced drug delivery systems.As their characteristics are mainly determined by their structures and compositions, strict quality control ought to be performed on TAGs, in order to guide their use in pharmaceutics. However, because of their complex compositions, no qualtity standard is set for TAGs in Ch.P currently.In this paper, we reviewed the methods for the separation and analysis of TAGs, includingthin-layer chromatog raphy, solid-phase extraction, gas chromotography, liquid chromatography, two-dimensional liquid chromatography,and ultraperformance convergence chromatography, and summarized their advantages and disadvantages.The application scope of each method was also overviewed in this review. Besides that we also pointed outthat according to our own study the newly emerged ultraperformance convergence chromatography would be one of the best methods to analyze TAGs.     

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??Pharmaceutical excipients are important ingredients of drugs, and the quality of it directly related to the safety of drug Compared to the 2010 edition, one of the most significant improvement of the 2015 edition of Chinese pharmacopoeia is the monographs of pharmaceutical excipients will be available in an individual book (Chinese Pharmacopoeia Book IV) And also, some new features will be found in the new edition??the doubled varieties of chronicled pharmaceutical excipients, the application of new techniques, the strict standards of the excipients for injection, the establishment of functionality??related characteristics This article will interpret the developing trend of the standards of pharmaceutical excipients and the effect of the trend on the entire pharmaceutical industry in the future via the improvement of Chinese Pharmacopoeia.     

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??OBJECTIVE To explore the stability of recombinant human serum albumin and interferon alpha 2b fusion protein for injection. METHODS According to the testing methods of Ch.P, influencing factors test [high temperature test at (42??2)??, strong light test at (4 500??500)lx and humidity test at RH of 90%], accelerated test (37 and 25 ??)and long-term test were carried out according to the technical guidelines of biological stability study. RESULTS The results of influencing factors test, accelerated test and long-term test showed that temperature had influence on the purity of products. The protein purity decreased with the increase of temperature. Humidity also had influence on the moisture content of products, with little influence on other indicators. Long term stability investigation found that the sample was relatively stable within 24 months and the examined indexes accorded with the quality standard. CONCLUSION This recombinant protein can be stored at 2-8 ?? for 24 months.     

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??Microbial control is one of the important parts of drug safety guarantee system. Chinese pharmacopoeia 2015 edition has constructed a complete system for pharmaceutical microbial control after continuous efforts since the 2005 edition. The new edition Chinese pharmacopoeia not only achieves the unity of three parts, but also makes harmonization between Chinese pharmacopoeia and ICH, thus is fully in line with international quality control system. In this paper, the revision progress of the last several editions of Chinese pharmacopoeia is reviewed. The main characteristics of pharmaceutical microbial control system in Chinese pharmacopoeia 2015 edition is clarified by revealing the formation process. The trend of this field in China is outlined by discussion on some hot issues.     

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??OBJECTIVE To introduce the application of the residual solvents determination methods in general chapter 0861 of Chinese pharmacopoeia 2015 edition. METHODS Determination of the residual solvents of cefathiamidine was chosen as an example to indicate that how to use the residual solvents determination methods in general chapter 0861 of Chinese pharmacopoeia 2015 edition when the methods for the determination of residual solvent in monograph of cefathiamidine did not work. RESULTS The residual solvents in cefathiamidine from different manufactures were determined accurately using methods in general chapter 0861 of Chinese pharmacopoeia 2015 edition. CONCLUSION The residual solvents determination methods in general chapter 0861 of Chinese pharmacopoeia 2015 can be used to screening and confirm the unknown peaks by the two opposite polar column systems, which can help to establish the residual solvents method.