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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 

High-performance liquid chromatography-mass spectrometric analysis of ramipril and its active metabolite ramiprilat in human serum: application to a pharmacokinetic study in the Chinese volunteers.

This study presents a rapid, specific and sensitive LC-MS/MS assay for the determination of ramipril and ramiprilat in human serum using enalapril as an internal standard (IS). A Waters Atlantis C18 column (2.1 mm x 100 mm, 3 microm) and a mobile phase consisting of 0.1% formic acid-methanol (25:75, v/v) were used for separation. The analysis was performed by the selected reaction monitoring (SRM) method, and the peak areas of the m/z 417.3-->234.3 and m/z 389.3-->206.2 transition for ramipril and ramiprilat, respectively, were measured versus that of the m/z 377.3-->234.2 for IS to generate the standard curves. The assay linearities of ramipril and ramiprilat were confirmed over the range 0.10-100 ngml(-1) and 0.25-100 ngml(-1), respectively, and limits of quantitation for them were 0.10 and 0.25 ngml(-1), respectively. The linear ranges correspond well with the serum concentrations of the analytes obtained in clinical pharmacokinetic studies. Intraday and interday relative standard deviations of ramipril and ramiprilat were 2.8-6.4% and 4.3-4.6%, 4.4-6.7% and 3.5-4.7%, respectively. The recoveries of ramipril and ramiprilat from serum were in the range of 81.0-98.2%. The developed LC-MS procedures were applied for the determination of the pharmacokinetic parameters of ramipril and ramiprilat following a single oral administration of 10mg ramipril tablets in 18 Chinese healthy male volunteers.[1]

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