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@#In this paper, the uncertainties of correction factors of fluconazole impurities determined by HPLC standard curve method were evaluated, and the main common factors affecting the accuracy of standard curve method were found, so as to improve the accuracy of the method.In this study, the corresponding fitting lines of fluconazole and its impurities A, B, C, D, F and I were established respectively, and the ratio of the slope of fitting lines of each impurity and its corresponding principal component was calculated as the correction factor of the impurity.Then on the basis of GUM method, the uncertainty of each impurity correction factor determined by standard curve method was evaluated according to the established uncertainty evaluation scheme of correction factor determination process.The correction factor and uncertainty of fluconazole impurities A, B, C, D, F and I were 1.068 ± 0.046, 0.102 ± 0.005, 0.0582 ± 0.0031, 1.382 ± 0.121, 0.802 ± 0.067 and 1.383 ± 0.119, respectively, and the coverage factor k was 2.Finally, the contribution rate of each uncertainty component was calculated.In the relative combined standard uncertainties urel(f) of fluconazole impurities A, B, C, D, F and I correction factors, the sum of contribution rate of slope uncertainty urel(K) of the linear equation of principal component and its impurity is more than 85%; in the slope uncertainties urel(K) of linear equation, the contribution rates of uncertainties of solution concentration in 8 of 12 data groups are more than 80%, and the contribution rates of uncertainties introduced by reference substance content in solution concentration are about 80%.It can be seen that the preparation of linear solution concentration is the most influential factor in the determination of impurity correction factor by standard curve method, followed by the linear fitting process.In the preparation process of linear solution concentration, the purity of reference substance is the most influential factor, followed by weighing and pipetting times.The conclusion can help the experimenters to better formulate experimental plans and ensure the accuracy of the results when doing similar work.
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Changes in structure of oral solid dosage forms (OSDF) elementally determine the drug release and its therapeutic effects. In this research, synchrotron radiation X-ray micro-computed tomography was utilized to visualize the 3D structure of enteric coated pellets recovered from the gastrointestinal tract of rats. The structures of pellets in solid state and in vitro compendium media were measured. Pellets in vivo underwent morphological and structural changes which differed significantly from those in vitro compendium media. Thus, optimizations of the dissolution media were performed to mimic the appropriate in vivo conditions by introducing pepsin and glass microspheres in media. The sphericity, pellet volume, pore volume and porosity of the in vivo esomeprazole magnesium pellets in stomach for 2 h were recorded 0.47, 1.55 × 108 μm3, 0.44 × 108 μm3 and 27.6%, respectively. After adding pepsin and glass microspheres, the above parameters in vitro reached to 0.44, 1.64 × 108 μm3, 0.38 × 108 μm3 and 23.0%, respectively. Omeprazole magnesium pellets behaved similarly. The structural features of pellets between in vitro media and in vivo condition were bridged successfully in terms of 3D structures to ensure better design, characterization and quality control of advanced OSDF.
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Objective:To evaluate the capacity and level of melting point determination of chemical drugs in the laboratories par-ticipating in the proficiency testing. Methods:Two test samples were prepared, and the labs volunteered to participate in the proficien-cy testing program ( PTP) . The melting point determination was performed according to the general principle 0612 in part four of Chi-nese Pharmacopoeia (2015 edition), and the results were analyzed by robust statistics and the determination proficiency of the laborato-ries were evaluated by Z-score. Results:The analysis showed that two test samples were homogeneous and stable, which met the re-quirements of the PTP. Totally 31 laboratories had satisfactory results, which accounted for 83. 8%. Conclusion:The majority of the participant laboratories can accurately determine the melting points of test samples, and the information is very helpful to the next profi-ciency testing program.
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Objective:To establish an HPLC method for the content determination of gliquidone tablets to improve the specificity of the content determination and the rationality of the preparation of test solution. Methods: A UPLC-MS system was used to analyze the degradation products with positive and negative ion scanning and sub-ion scanning. An ACQUITY UPLC BEH C18 column(2. 1 mm × 50 mm,1. 7 μm) was employed with the mobile phase consisting of water (adjustting pH to 3. 5 with formic acid)-acetonitrile with gradient elution. The HPLC method was performed on an Agilent Zorbax SB-C18 column(150 mm × 4. 6 mm,5 μm). Water (adjusing pH to 3. 5 with formic acid)-acetonitrile(37. 5∶62. 5) was used as the mobile phase. The detection wavelength was set at 230 nm. The column temperature was set at 30℃. The flow rate was 1. 0 ml·min-1 with the injection volume of 20μl. Results:A good linear re-lationship was obtained within the range of 60. 200-140. 400μg·ml-1(r=0. 999 5), and the average recovery was 98. 60% with RSD of 0. 6% (n=9). Conclusion:The method is accurate, reliable, specific and reproducible, which can be used in the determination of content and content uniformity of gliquidone tablets.
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Objective:To analyze and evaluate the degassing effect of vacuum degassing apparatus through the determination of ox-ygen content in pure water, gas pressure and air volume, and compare with suction filtration, boiling and ultrasonic methods to choose the appropriate degassing method for dissolution medium and guide the daily inspection work. Methods: The water residual oxygen, gas pressure and air volume were determined using a single water quality on-line monitoring instrument and a Carbo QC Anton Pear in-strument. The degassing effect of the vacuum degassing apparatus was detected under the conditions of negative pressure and certain de-gassing time. The degassing effect was also compared with that of suction filter, boiling and ultrasonic methods. Results: Under the conditions of 0. 06 MPa negative pressure, 41℃ medium temperature and 30 min degassing time, the degassing effect of the vacuum degassing apparatus was obvious. The degassing effect of suction filter and boiling methods was similar to that of the vacuum degassing apparatus, while that of ultrasonic method wasn't obvious. Conclusion:The use of vacuum degassing apparatus is simple and efficient with obvious degassing effect, which is suitable for the degassing process of dissolution medium.
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HPLC is widely applied in the analysis of chemical drugs. In order to regulate the use and maintenance of HPLC col-umn and guarantee the analysis quality of HPLC, the classified management of HPLC column was explored in the paper from the follow-ing five aspects:file establishment, recipient and return management, column performance evaluation, information accumulation of ap-plication range, and maintenance and abandonment of HPLC column.