کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
7616967 | 1494053 | 2015 | 42 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Regulated bioanalysis of conformers - A case study with ASP2151 in dog plasma and urine
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کلمات کلیدی
موضوعات مرتبط
مهندسی و علوم پایه
شیمی
شیمی آنالیزی یا شیمی تجزیه
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چکیده انگلیسی
We developed and validated bioanalytical methods for a potent helicase-primase inhibitor ASP2151 that has two conformers. These conformers elute as unseparated broad peaks under ordinary high-performance liquid chromatographic conditions, indicating discernable differences in hydrophobicity. We observed that column temperature and mobile phase pH have no effect on these peaks and that conformers form a single symmetrical peak when tetrahydrofuran is added to the mobile phase. In addition, we needed to develop semi-automated methods where inter-conversion of the conformers is unlikely to cause sample-to-sample extraction variability. Briefly, following the addition of deuterium-labeled ASP2151 as an internal standard (IS), dog plasma samples or acetonitrile-added urine samples were filtrated. The filtrates were then injected into a column-switching liquid chromatography-tandem mass spectrometry (LC-MS/MS) system and trapped onto an extraction column. Extracts were back-flushed onto an analytical C18 column (4.6 Ã 50 mm, 3 μm) with a mobile phase consisting of methanol, tetrahydrofuran, and 20 mmol/L ammonium acetate (45:5:50, v/v/v). The eluent was monitored in the negative atmospheric pressure chemical ionization mode. The calibration curve was linear over a range of 5-1000 ng/mL for plasma and 0.5-100 μg/mL for urine. Validation data met the acceptance criteria in accordance with regulatory guidance and demonstrated that these methods were selective, accurate, and reproducible. In addition, the present methods were successfully applied to a pharmacokinetic study in dogs.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Chromatography B - Volume 997, 1 August 2015, Pages 56-63
Journal: Journal of Chromatography B - Volume 997, 1 August 2015, Pages 56-63
نویسندگان
Yoshiaki Ohtsu, Shohei Otsuka, Takeshi Nakamura, Kiyoshi Noguchi,