کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1212859 1494091 2014 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Quantitative analysis of erythromycylamine in human plasma by liquid chromatography-tandem mass spectrometry and its application in a bioequivalence study of dirithromycin enteric-coated tablets with a special focus on the fragmentation pattern and carryo
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آنالیزی یا شیمی تجزیه
پیش نمایش صفحه اول مقاله
Quantitative analysis of erythromycylamine in human plasma by liquid chromatography-tandem mass spectrometry and its application in a bioequivalence study of dirithromycin enteric-coated tablets with a special focus on the fragmentation pattern and carryo
چکیده انگلیسی


• An LC–MS/MS method was developed for erythromycylamine determination.
• The fragmentation pattern of erythromycylamine and IS azithromycin were investigated.
• The transitions from double-charged ion to sugar moiety were chosen for analyses.
• We optimize the mobile phase and use special needle wash to eliminate carryover effects.
• We carried out a rapid SPE procedure followed by dilution for sample purification.

A liquid chromatography-tandem mass spectrometry method was developed and validated for the quantification of erythromycylamine, which is the predominant active metabolite of dirithromycin in human plasma. After solid-phase extraction, the analyte and internal standard (IS) were separated by using an isocratic mobile phase consisting of 20 mM ammonium acetate (pH 3.9, adjusted with formic acid)-acetonitrile (75:25, v/v) on a Phenyl–Hexyl column (150 × 2.1 mm, 3 μm) and then analyzed in positive ion mode under electrospray ionization. Azithromycin was selected as the IS because it has the most similar mass spectrometric and chromatographic behaviors to the analyte. The respective multiple reaction monitoring (MRM) transitions, m/z 368.5 > 83.2 for erythromycylamine and m/z 375.4 > 115.2 for IS were chosen to achieve high sensitivity and selectivity in determination. A more acidic mobile phase (pH 3.9) than those of previous reports and a special needle wash (ethylene glycol-acetonitrile-water, 50:30:20, v/v/v, adjusted to pH 3.9 using formic acid) were used to eliminate the carryover effects of the two macrolides. The method exhibited a linear dynamic range of 0.5–440.0 ng/mL for erythromycylamine in human plasma (r = 0.9999). The lower limit of quantification (LLOQ) and limit of detection (LOD) were 0.5 and 0.05 ng/mL, respectively. The mean extraction recoveries were higher than 94.0% for the analyte and IS. The intra- and inter-day precisions ranged from 1.4 to 5.4% and from 1.6 to 4.0%, respectively. The accuracy varied between 91.2 and 101.2%. The established method was successfully applied to analyze the human plasma samples from 24 healthy subjects in a bioequivalence study of two dirithromycin enteric-coated formulations.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Chromatography B - Volumes 947–948, 1 February 2014, Pages 156–163
نویسندگان
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