| 20044316 |
Zhang X, Duan J, Zhai S, Yang Y, Yang L: Performance of tiloronoxim and tilorone determination in human blood by HPLC-MS/MS: method validation, uncertainty assessment and its application to a pharmacokinetic study. J Chromatogr B Analyt Technol Biomed Life Sci. 2010 Feb 1;878(3-4):492-6. Epub 2009 Dec 21.
A highly sensitive and selective HPLC-MS/MS method is presented for the quantitative determination of tiloronoxim and its metabolite tilorone in human blood. An aliquot of 200 microl human blood was extracted with a mixture of chloroform/ethyl ether (1/2, v/v), using metoprolol as the internal standard (the IS). Separation was achieved on an Xterra MS C18 column (50 mm x 2.1 mm, 5 microm) with a gradient mobile phase of methanol/water containing 15 mM ammonium bicarbonate (pH 10.5). Detection was performed using positive MRM mode on a TurboIonSpray source. The mass transitions monitored were m/z 426.3--> 100.0, m/z 411.3--> 100.0 and m/z 268.3--> 116.1 for tiloronoxim, tilorone and the IS, respectively. The method was fully validated using total error theory, which is based on beta-expectation tolerance intervals and include trueness and intermediate precision. The method was found to be accurate over a concentration range of 1-100 ng/ml for both compounds. The measurement uncertainty based on beta-expectation tolerance intervals was assessed at each concentration level of the validation standards. This method was successively applied to a pharmacokinetic study of tiloronoxim in healthy volunteers. |
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