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Development of HPLC-CAD method for simultaneous quantification of nine related substances in ursodeoxycholic acid and identification of two unknown impurities by HPLC-Q-TOF-MS.
Huang, Yiwen; Lu, Hui; Li, Zhong; Zeng, Yuan; Xu, Qi; Wu, Yang.
  • Huang Y; Suzhou Institute for Drug Control, Suzhou 215104, China.
  • Lu H; Suzhou Institute for Drug Control, Suzhou 215104, China.
  • Li Z; Yantai Institute of Materia Medica, Yantai Branch, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Yantai 264000, China.
  • Zeng Y; Clinical Pharmacology & Bioanalytics, Development China, Pfizer Pharmaceutical Ltd., Shanghai 201210, China.
  • Xu Q; Suzhou Institute for Drug Control, Suzhou 215104, China.
  • Wu Y; Suzhou Institute for Drug Control, Suzhou 215104, China. Electronic address: wuyang216217@163.com.
J Pharm Biomed Anal ; 229: 115357, 2023 May 30.
Article in English | MEDLINE | ID: covidwho-2263488
ABSTRACT
Ursodeoxycholic acid has gained increasing attention due to its recent discovery of the preventive effect on SARS-CoV-2 infection. Ursodeoxycholic acid has been included in various pharmacopoeias as an old drug, and the latest European Pharmacopoeia lists nine potential related substances (impurities A∼I). However, existing methods in pharmacopoeias and literature can only quantify up to five of these impurities simultaneously, and the sensitivity is inadequate, as the impurities are isomers or cholic acid analogues lacking chromophores. Herein, a novel gradient RP-HPLC method coupled to charged aerosol detection (CAD) was developed and validated for the simultaneous separation and quantification of the nine impurities in ursodeoxycholic acid. The method proved sensitive and allowed the quantification of the impurities as low as 0.02 %. Relative correction factors of the nine impurities were all within the range of 0.8-1.2 in the gradient mode by optimizing chromatographic conditions and CAD parameters. In addition, this RP-HPLC method is fully compatible with LC-MS due to the volatile additives and high percentage of the organic phase, which can be directly used for the identification of impurities. The newly developed HPLC-CAD method was successfully applied to commercial bulk drug samples, and two unknown impurities were identified by HPLC-Q-TOF-MS. The effect of CAD parameters on the linearity and correction factors was also discussed in this study. Overall, the established HPLC-CAD method can improve the methods in current pharmacopoeias and literature and contributes to understanding the impurity profile for process improvement.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Ursodeoxycholic Acid / COVID-19 Type of study: Diagnostic study / Prognostic study Limits: Humans Language: English Journal: J Pharm Biomed Anal Year: 2023 Document Type: Article Affiliation country: J.jpba.2023.115357

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Ursodeoxycholic Acid / COVID-19 Type of study: Diagnostic study / Prognostic study Limits: Humans Language: English Journal: J Pharm Biomed Anal Year: 2023 Document Type: Article Affiliation country: J.jpba.2023.115357