Development and Validation of Atorvastatin by LC-ESI-MS and Application in Bioequivalence Research in Healthy Chinese Volunteers

• Published in: Chromatographia Vol. 65; no. 11-12; pp. 737 - 741
• Main Authors: Ma, L, Dong, J, Chen, X. J, Wang, G. J
• Format: Journal Article
• Language: English
• Published: Oxford Wiesbaden : Vieweg Verlag 01.06.2007; Springer; Springer Nature B.V
• Subjects: Analysis; Atorvastatin; Bioequivalence; Biological and medical sciences; Blood plasma; Correlation coefficients; electrospray ionization mass spectrometry; Ethyl acetate; General pharmacology; humans; LC-ESI-MS; liquid chromatography; Medical sciences; Pharmacokinetics; Pharmacology; Pharmacology. Drug treatments; reversed-phase liquid chromatography; Spectrometry; volunteers; Asia; China; Human; Validation; Column liquid chromatography; Chemical analysis; Bioequivalence; LC-ESI-MS; Enzyme; Coupled method; Volunteer; Oral administration; Enzyme inhibitor; HPLC chromatography; Statin derivative; Normal; Electrospray; Reversed phase chromatography; Atorvastatin; Hydroxymethylglutaryl-CoA reductase; Oxidoreductases; Pharmacokinetics; Mass spectrometry; Quantitative analysis; Antilipemic agent
• ISSN: 0009-5893; 1612-1112
• DOI: 10.1365/s10337-007-0236-4

The aim of this research was to develop a sensitive liquid chromatographic-electrospray ionization-mass spectrometric (LC-MS) method for direct measurement of the concentration of Atorvastatin in human plasma. Plasma samples (1 mL) were extracted with 3 mL ethyl acetate, and by a simple reversed-phase chromatography. Pitavastatin was used as internal standard (IS). The LOQ was 0.25 ng mL-¹ (RSD 4.24%). The assay was linear from 0.25-20 ng mL-¹. And the correlation coefficient for the calibration regression line was 0.9996 or better. Intra-day and inter-day accuracy were better than 15%. The method has been successfully used for a pharmacokinetic study with human subjects. A two-period crossover designed bioequivalence research was also progressed in healthy Chinese volunteers. Among the pharmacokinetic data obtained, T max was 1.36 ± 0.68 h for reference formulation and 0.81 ± 0.54 h for test formulation. C max was 8.54 ± 5.06 ng mL-¹ for reference formulation and 9.54 ± 3.68 ng mL-¹ for test formulation. t ₁/₂ was 8.50 ± 2.74 h for reference formulation and 9.24 ± 3.17 h for test formulation. AUC ₀-₄₈h was 54.77 ± 21.82 h ng mL-¹ for reference formulation and 55.66 ± 20.91 h ng mL-¹ for test formulation. The method was successfully applied to the study of pharmacokinetics of Atorvastatin in healthy Chinese volunteers.