کد مقاله کد نشریه سال انتشار مقاله انگلیسی ترجمه فارسی نسخه تمام متن
5137984 1494592 2017 25 صفحه PDF سفارش دهید دانلود رایگان
عنوان انگلیسی مقاله ISI
Development and validation of an ultra-performance liquid chromatography-tandem mass spectrometry method for quantification of SR1001, an inverse agonist of retinoid-related orphan receptors, and its application to pharmacokinetic studies in streptozotoci
دانلود مقاله + سفارش ترجمه
دانلود مقاله ISI انگلیسی
رایگان برای ایرانیان
سفارش ترجمه تخصصی
با تضمین قیمت و کیفیت
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آنالیزی یا شیمی تجزیه
پیش نمایش صفحه اول مقاله
Development and validation of an ultra-performance liquid chromatography-tandem mass spectrometry method for quantification of SR1001, an inverse agonist of retinoid-related orphan receptors, and its application to pharmacokinetic studies in streptozotoci
چکیده انگلیسی
Retinoic acid receptor-related orphan receptors (RORs) play critical roles in the onset and progression of type I diabetes, an autoimmune disease characterized by the destruction of pancreatic β-cells. SR1001, an ROR inverse agonist, has been proven to be an effective diabetes treatment in the non-obese diabetic (NOD) mouse model. However, optimization of this treatment is challenging because knowledge of SR1001 pharmacokinetic (PK) behaviors in type I diabetic animals is limited. The aim of our study was to develop and validate a specific and sensitive ultra-performance liquid chromatography-tandem mass spectrometric (UPLC-MS/MS) method to measure the concentrations of SR1001 in plasma and biological samples. Using the developed UPLC-MS/MS method, SR1001 linearity ranges in biological matrices were determined to be 5-1000 ng/mL, with correlation coefficients of >0.99. The limit of detection (LOD) and limit of quantification (LOQ) values of SR1001 were 1 and 5 ng/mL, respectively. And the intra-day and inter-day variances were less than 10%, and accuracy was within 90%-110%. The extraction recoveries of SR1001 were ≥80%, and no significant matrix effect was observed. Using the validated UPLC-MS/MS method, levels of SR1001 in plasma and six major organs (heart, liver, spleen, lung, kidney, and brain) were determined in streptozotocin (STZ) −induced diabetic mice. The PK parameters of SR1001 were also calculated. The SR1001 drug concentration-time curves for organs and plasma showed similar trends, and the elimination half-lives of SR1001 in diabetic mice were about 12 h. SR1001 was highly bound to plasma protein, resulting in a much higher maximum concentration (Cmax = 144394 ng/mL) and area under the concentration-time curve (AUC0-t = 2728258 ng/mL*h), but a low tissue/plasma partition coefficient (Kp) value of <0.3.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Pharmaceutical and Biomedical Analysis - Volume 143, 5 September 2017, Pages 94-100
نویسندگان
, , , , , , , , , ,
دانلود مقاله + سفارش ترجمه
دانلود مقاله ISI انگلیسی
رایگان برای ایرانیان
سفارش ترجمه تخصصی
با تضمین قیمت و کیفیت