HPLC标准曲线法测定氟康唑杂质校正因子的测量不确定度评定
Evaluation on measurement uncertainty of correction factors of fluconazole impurities determined by HPLC standard curve method
-
摘要: 通过对HPLC标准曲线法测定氟康唑杂质校正因子的实验过程进行不确定度评定，探索影响杂质校正因子测定准确性的主要共性因素，为提高测定结果的准确性提供研究思路。首先分别建立了氟康唑及其杂质A、B、C、D、F、I相应的拟合直线，计算各杂质及其对应主成分的拟合直线斜率之比作为该杂质的校正因子。接着以GUM法为基础，根据已经建立的校正因子测定过程的不确定度评定方案，分别计算得到标准曲线法测定各杂质校正因子的不确定度。氟康唑杂质A、B、C、D、F、I校正因子分别为 1.068 ± 0.046、0.102 ± 0.005、0.0582 ± 0.003、1.382 ± 0.121、0.802 ± 0.067和1.383 ± 0.119，其中包含因子k = 2。最后计算各不确定度分量的贡献率，氟康唑杂质A、B、C、D、F、I校正因子测定的相对合成标准不确定度urel（f）中主成分和杂质的线性方程斜率不确定度urel（K）贡献率之和占比均大于85%；在线性方程斜率不确定度urel（K）中，12组数据中的8组溶液浓度不确定度贡献率占比在80%以上，其中由对照品含量在溶液浓度中引入的不确定度贡献率约为80%。由此可见，标准曲线法测定杂质校正因子的过程中线性溶液浓度的配制是最大影响因素，其次是直线拟合过程；在线性溶液浓度配制过程中对照品的纯度是最大影响因素，其次是称量和移液次数。该结论的得出可以帮助实验人员在从事类似工作时更好的制定实验方案，保障结果的准确性。Abstract: 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.
-
-
[1] . Beijing：China Medical Science and Technology Press，2020：64. [2] The United States Pharmacopeial Convention. United States Pharmacopoeia：volume 5［S］. Baltimore：United Book Press ［S］. 2019：8047.[3] Yu ZX，Yu LJ，Huang HW，et al. Discussion on the calculation methods of the known impurities in related substances determined by HPLC［J］. Drug Stand China（中国药品标准），2010，11（4）：278-282. [4] Xiao T，Wang C，Yao SC，et al. Application of an HPLC correction factor method in pharmaceutical analysis［J］. Acta Pharm Sin（药学学报），2020，55（12）：2854-2861. [5] Wang K，Sun P，Ma Y，et al. Determination of diketo aldehyde in dihydroartemisinin bulk drug by principal component reference substances external standard method with correction factor［J］. Chin Pharm J（中国药学杂志），2020，55（1）：52-57. [6] Gu YP，Yang Y，Li M，et al. Research and determination of related substances in trapidil［J］. Chin J Pharm Anal（药物分析杂志），2021，41（12）：2122-2131. [7] Liu P，Hu LM，Tian HN，et al. HPLC method for determination of hydroxylated cefaclor impurities［J］. Chin J Antibiot（中国抗生素杂志），2022，47（1）：48-54. [8] Ni YC. Practical Evaluation of Measurement Uncertainty（实用测量不确定度评定）［M］. 5th ed . Beijing：China Quality Inspection Press and China Standards Press，2016：15-83.[9] Chai ZL，Yuan CX，Zhou XK，et al. Measurement uncertainty was evaluated in determination of profenofos （PFF） residues in cucumber by gas chromatography（GC）［J］. Sci Technol Food Ind（食品工业科技），2020，41（12）：238-244. [10] Xiao T，Wang C，Yao SC，et al. Evaluation on measurement uncertainty of impurity correction factor determined by HPLC standard curve method［J］. Chin J Antibiot（中国抗生素杂志），2021，46（4）：271-278. [11] Wan K，Zhang YY，Zhou CH，et al. Recent advances in antifungal fluconazole［J］. Chin J Antibiot（中国抗生素杂志），2012，37（1）：8-20. [12] Yao SC，Chang Y，Hu CQ. Study of uncertainty of β-lactam antibiotics chemical reference substance being used in HPLC［J］. Chin J Pharm Anal（药物分析杂志），2010，30（11）：2104-2110. [13] Liu SY，Hu CQ. A comparative uncertainty study of the calibration of macrolide antibiotic reference standards using quantitative nuclear magnetic resonance and mass balance methods［J］. Anal Chim Acta，2007，602（1）：114-121. -
期刊类型引用(8)
1. 刘健弘，张欣橦，李颖娴，杨展，符艺，周瑜芳. 药物缓释体系的研究进展. 广东化工. 2024(15): 90-92+45 . 
百度学术
2. 郑丽君，刘玲，张向荣. 脂质体在乳品中的应用. 中国药剂学杂志(网络版). 2023(01): 34-48 . 百度学术
3. 郭文娣，彭玉帅，许卉，陈华. 脂质体制剂制备工艺及质量控制研究进展. 药物分析杂志. 2023(01): 61-69 . 百度学术
4. 柳宇红，姜宇，郝贵周，刘善奎. 挤出法制备卡巴他赛脂质体的工艺优化. 药学研究. 2023(04): 243-246+284 . 百度学术
5. 吴灿，关延彬，贾永艳. 药剂学课程思政探索——以“脂质体”为例. 中国教育技术装备. 2023(18): 72-74 . 百度学术
6. 毛欣亮，邓惠林，张浩，李吉平，蔡德富，樊丽，孙珈，岳丽玲，潘思文，温宪春. 共载紫草素和盐酸阿霉素pH敏感脂质体的制备及理化性质评价. 齐齐哈尔医学院学报. 2023(23): 2201-2207 . 百度学术
7. 蔡成龙，闫雪生，于蓓蓓，孙丹丹. 透明质酸修饰茯苓皮总三萜脂质体制备与表征研究. 辽宁中医药大学学报. 2022(05): 50-55 . 百度学术
8. 张艺，杭太俊，宋敏. 载药脂质体包封率测定方法的研究进展. 中国药科大学学报. 2021(02): 245-252 . 本站查看
其他类型引用(12)
计量
- 文章访问数: 154
- HTML全文浏览量: 12
- PDF下载量: 343
- 被引次数: 20
下载:
