کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8309467 | 1538614 | 2018 | 7 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Investigation of metabolic degradation of new ALK inhibitor: Entrectinib by LC-MS/MS
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Investigation of metabolic degradation of new ALK inhibitor: Entrectinib by LC-MS/MS Investigation of metabolic degradation of new ALK inhibitor: Entrectinib by LC-MS/MS](/preview/png/8309467.png)
چکیده انگلیسی
Entrectinib (ENC) is a potent orally available anaplastic lymphoma kinase (ALK) inhibitor. In 10 July 2017, biotechnology company (Ignyta) announced that granted orphan drug designation approval was given by the FDA to ENC for “treatment of NTRK fusion-positive solid tumors”. A validated LC-MS/MS methodology was developed for ENC quantification in human plasma matrix. The supposed method characterized by high speed, specificity and sensitivity. This established method was applied for metabolic degradation assessment of ENC. Reversed stationary phase (C18 column) and elution mobile phase (48% 10â¯mM ammonium formate in H2O (pH: 4.2 adjusted by adding few drops of formic acid): 52% ACN) were utilized for chromatographic resolution of ENC and lapatinib as internal standard (IS). Total elution time, flow rate and injection volume were 4â¯min., 0.25â¯mL/min., and 5â¯Î¼L, respectively. Electrospray ionization source was used for ions generation, while positive multiple reactions monitoring (MRM) mode was used for ion analysis. The data of calibration curve of ENC in human plasma was linear in the range of 5-500â¯ng/mL with correlation coefficient (r2) >0.999. LOQ and LOD for ENC were 2.17â¯ng/mL and 0.71â¯ng/mL, respectively. Inter-day and intra-day precision and accuracy were 97.52 to 101.83%, and 0.38 to 1.32%, respectively. Intrinsic clearance (Clint) and in vitro half-life (t1/2) were equal to 15.67â¯mL/min/kg and 9.1â¯min, respectively. To our knowledge, this is considered the first method for ENC quantification in human plasma and its metabolic degradation assessment.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Clinica Chimica Acta - Volume 485, October 2018, Pages 298-304
Journal: Clinica Chimica Acta - Volume 485, October 2018, Pages 298-304
نویسندگان
Mohamed W. Attwa, Hany W. Darwish, Hassan A. Alhazmi, Adnan A. Kadi,