کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1216795 1494127 2012 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Development and validation of a RP-HPLC method with fluorescence detection for simultaneous determination of 10-methoxycamptothecin and its metabolite 10-hydroxycamptothecin in rat plasma
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آنالیزی یا شیمی تجزیه
پیش نمایش صفحه اول مقاله
Development and validation of a RP-HPLC method with fluorescence detection for simultaneous determination of 10-methoxycamptothecin and its metabolite 10-hydroxycamptothecin in rat plasma
چکیده انگلیسی

Both 10-methoxycamptothecin (MCPT) and 10-hydroxycamptothecin (HCPT) are the natural bioactive derivatives of camptothecin (CPT) isolated from Camptotheca acuminata, and have been confirmed to possess high anti-cancer properties. In the present study, HCPT was identified as the major metabolite of MCPT in rat plasma through HPLC/photodiode array detection (PDA) and LC–MS/MS analysis. A sensitive and reliable RP-HPLC method with fluorescence detection was developed and validated for the simultaneous analysis of MCPT and HCPT in rat plasma. The parental CPT was used as an internal standard (IS). A piecewise linear function was used over lower and higher concentrations, respectively. The calibration curves were linear (r2 > 0.999) over concentrations from 1.25 to 20 ng/mL and 20 to 320 ng/mL for both MCPT and HCPT. The method had an accuracy of 92.24–113.90%, and the intra- and inter-day precision (RSD%) were 10.05% or less for MCPT and HCPT. The stability data showed no significant degradation occurred under the experimental conditions. The mean recoveries at concentrations of 2.5, 40 and 160 ng/mL were 95.09 ± 3.94%, 98.67 ± 1.40% and 95.65 ± 2.15% for MCPT and 84.06 ± 4.39%, 84.85 ± 3.10% and 81.03 ± 4.44% for HCPT, respectively. The lower limit of quantification (LLOQ) using 0.1 mL of plasma was 1.25 ng/mL for both MCPT and HCPT. This method was successfully applied to the pharmacokinetic study of MCPT and its metabolite HCPT in rat plasma after intravenous administration.


► 10-Methoxycamptothecin (MCPT) shows very high cytotoxicity against 2774 cell lines.
► 10-Hydroxycamptothecin (HCPT) was identified as a metabolite of MCPT in rat plasma.
► A RP-HPLC method was developed for simultaneous analysis of MCPT and HCPT.
► MCPT may mainly metabolize to HCPT in rats plasma after i.v. administration.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Chromatography B - Volume 903, 15 August 2012, Pages 81–87
نویسندگان
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