کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1224951 967940 2006 6 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Quantitation of geometric isomers of a phosphodiesterase inhibitor in rat and monkey plasma using liquid chromatography-tandem mass spectrometry
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آنالیزی یا شیمی تجزیه
پیش نمایش صفحه اول مقاله
Quantitation of geometric isomers of a phosphodiesterase inhibitor in rat and monkey plasma using liquid chromatography-tandem mass spectrometry
چکیده انگلیسی
Quantitation of geometric isomers of a phosphodiesterase inhibitor was required to determine the extent of interconversion following dosing of a single isomer in preclinical pharmacokinetic studies. Assays were developed for the simultaneous determination of Compound A (Fig. 1), 6-[1-methyl-1-(methylsulfonyl)ethyl-8(3-{(E)-2-(3-methyl-1,2,4-oxadiazol-5-yl)-2-[4-(methylsulfonyl)phenyl]ethenyl}phenyl)quinoline] and its geometric Z-isomer, Compound B, in plasma using liquid chromatography-tandem mass spectrometry. Sample clean-up was performed using a semi-automated liquid-liquid extraction procedure. Separation was achieved on a Phenomenex Synergi MAX-RP column. The method was validated in the linear range of 2-2000 ng/mL for Compound A and 0.5-500 ng/mL for Compound B in plasma and successfully applied to preclinical pharmacokinetic studies. Compound A was dosed in rats and Compound B in monkeys and the degree of conversion was determined by comparing the area under the curve. The relative amount of conversion was less than 1 and 10% in rats and monkeys, respectively. Because of the small amount of conversion and minor peak tailing of the dosed geometric isomer, the order of elution of the two analytes was important in order to achieve best quantitative results. The minor component needs to elute first; thus, a second assay was developed in which the order of elution was reversed. This was achieved by changing the mobile phase modifier.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Pharmaceutical and Biomedical Analysis - Volume 41, Issue 4, 16 June 2006, Pages 1293-1298
نویسندگان
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