کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1212160 1494057 2015 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Development and validation of LC–MS/MS assay for the determination of the prodrug Midodrine and its active metabolite Desglymidodrine in plasma of ascitic patients: Application to individualized therapy and comparative pharmacokinetics
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آنالیزی یا شیمی تجزیه
پیش نمایش صفحه اول مقاله
Development and validation of LC–MS/MS assay for the determination of the prodrug Midodrine and its active metabolite Desglymidodrine in plasma of ascitic patients: Application to individualized therapy and comparative pharmacokinetics
چکیده انگلیسی


• LC–MS/MS for determination of Midodrine and its active metabolite.
• Comparative pharmacokinetics: healthy volunteers vs ascitic patients with liver cirrhosis.
• The assay is applicable for therapeutic drug monitoring and individualized therapy.

Midodrine (MD) is a prodrug that is converted after oral administration to Desglymidodrine (DMD). In this study, an LC–MS/MS assay was developed and validated for investigation of the pharmacokinetics of MD and DMD in non azotemic patients with liver cirrhosis and tense ascites. Results were compared to those noted with healthy volunteers following the adminstration of a single oral dose of MD. Sample preparation was performed by liquid–liquid extraction using t-butyl methyl ether. HPLC separation was carried out using RP C18 column (4.6 mm × 50 mm, 5 μm). Isocratic elution was performed using methanol:0.2% formic acid (70:30, v/v) as the mobile phase, at a flow rate of 0.7 mL/min. Tandem mass spectrometric detection was employed at positive electrospray ionization in MRM mode for the determination of MD and DMD. Analysis was carried out within 1.0 min over a concentration range of 0.50–40.00 ng/mL for the prodrug and its active metabolite. The assay was validated according to FDA guidelines for bioanalytical method validation and satisfactory results were obtained. The applicability of the assay for the determination of the pharmacokinetic parameters of MD and DMD and personalized therapy was demonstrated in healthy volunteers and ascitic patients. Results revealed significant differences in pharmacokinetic parameters among the studied groups. Such differences were explained on the basis of the medical condition and co-adminstered medications exerting possible drug–drug interaction. Results confirmed the need for implementation of reliable analysis tools for therapeutic dose adjustment.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Chromatography B - Volume 991, 1 June 2015, Pages 34–40
نویسندگان
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