کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2480587 1556197 2014 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Identification of metabolites of fosinopril produced by human and rat liver microsomes with liquid chromatography–mass spectrometry
ترجمه فارسی عنوان
شناسایی متابولیت های فوزینوپریل تولید شده توسط میکروسوم های کبدی انسان و موش با دستگاه اسپکترومتری جرمی کروماتوگرافی
موضوعات مرتبط
علوم پزشکی و سلامت داروسازی، سم شناسی و علوم دارویی اکتشاف دارویی
چکیده انگلیسی

Metabolic profiles of prodrug fosinopril and pharmacologically active metabolite fosinoprilat were studied using human or rat liver microsomes and S9 fractions. Metabolites were identified by ultra high-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UHPLC/Q-TOF-MS) using electrospray ionization in the positive and negative ion mode. They were characterized by accurate MS and MS/MS spectra and based on their different fragmentation pathways. With human liver microsomes fosinopril was metabolized via hydroxylation, glucuronidation, and hydrolysis to fosinoprilat. As expected the main metabolite was fosinoprilat and it was further hydroxylated and glucuronidated. However, these metabolites were not detected after incubation of fosinoprilat with human liver microsomes, indicating that metabolic reactions occur in sequence and fosinopril is hydrolyzed after glucuronidation or hydroxylation. With the developed UHPLC/Q-TOF-MS method once or twice hydroxylated fosinopril metabolites were detected for the first time and different regioisomers were separated. It was observed that the hydrolysis of fosinopril to fosinoprilat was more efficient with rat than with human liver microsomes, and therefore more hydroxylated fosinoprilat metabolites were detected when rat liver microsomes were used. Glucuronidation of fosinopril was not observed with rat liver microsomes.

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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: European Journal of Pharmaceutical Sciences - Volume 53, 12 March 2014, Pages 86–94
نویسندگان
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