کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
7626567 | 1494580 | 2018 | 24 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Simple and sensitive LC-MS/MS method for simultaneous determination of crizotinib and its major oxidative metabolite in human plasma: Application to a clinical pharmacokinetic study
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موضوعات مرتبط
مهندسی و علوم پایه
شیمی
شیمی آنالیزی یا شیمی تجزیه
پیش نمایش صفحه اول مقاله

چکیده انگلیسی
In this study, a fast, simple and sensitive liquid chromatography-mass spectrometry method was developed for simultaneous determination of crizotinib and its major oxidative metabolite crizotinib-lactam in human plasma. The plasma samples were deproteinated by using acetonitrile containing 0.1% formic acid as precipitant whereas the chromatographic separation was obtained on a C18 column with 0.1% formic acid aqueous and acetonitrile/methanol (v:v, 1:1) as mobile phase. The mass detector was operated in positive selected reaction monitoring mode. Precursor-to-product transitions were optimized to be m/z 450.1/260.1, m/z 464.1/98.1, and m/z 326.1/291.1 for crizotinib, crizotinib-lactam and midazolam (internal standard), respectively. The established method was validated in accordance with guidance issued by Food and Drug Administration. The assay showed good linearity over the concentration ranges of 0.1-1000â¯ng/mL for crizotinib and 0.1-400â¯ng/mL for crizotinib-lactam, with correlation coefficients more than 0.999 (râ¯>â¯0.999). The extraction recovery was more than 87.12%. No significant matrix effect and carryover were observed. The precision (RSD, %) was less than 8.27%, whereas accuracy (RE, %) was within the range of â4.56 to 7.08%. The validated method has been successfully applied to the clinical pharmacokinetic study of crizotinib and crizotinib-lactam in human plasma after oral administration of crizotinib at a single dose of 250â¯mg. The results revealed that crizotinib was rapidly metabolized into its metabolite crizotinib-lactam and the in vivo exposure of crizotinib-lactam was 38.50% of that of crizotinib.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Pharmaceutical and Biomedical Analysis - Volume 155, 5 June 2018, Pages 210-215
Journal: Journal of Pharmaceutical and Biomedical Analysis - Volume 155, 5 June 2018, Pages 210-215
نویسندگان
Xiaoyan Qi, Lin Zhao, Qiuping Zhao, Qiaoxia Xu,