کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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1201834 | 1493684 | 2012 | 8 صفحه PDF | دانلود رایگان |
A liquid chromatography–tandem mass spectrometry (LC–MS/MS) method was developed for simultaneous quantification of mycophenolic acid (MPA) and its phenolic glucuronide (MPAG) in saliva and plasma. Saliva was collected and processed using a standardized commercially available collection device. Sample preparation comprised of protein precipitation with acetonitrile and subsequent centrifugation, followed by evaporation and reconstitution with mobile phase. A labeled isotope of MPA was used as internal standard, and chromatographic separation was achieved on a C18 column with an isocratic flow. LC–MS/MS detection was performed using a triple-stage quadrupole mass spectrometer working in selected reaction monitoring mode with positive electrospray ionization (ESI). The analytes were quantified in a single run within 2 min. For saliva, linearity was demonstrated over the concentration range of 5.0 to 400.0 ng/ml for both MPA and MPAG, and from 0.08 to 20.00 μg/ml for MPA and 0.4 to 100.0 μg/ml for MPAG in plasma. The lower limits of quantification for MPA and MPAG were 0.07 and 0.80 ng/ml in saliva, and 0.002 and 0.009 μg/ml in plasma, respectively. Inter- and intra-day precisions expressed as relative standard deviation (RSD) and accuracies were less than 15%. The recoveries for MPA and MPAG from the collection device's swab were higher than 90%. Sample stability was confirmed for bench times up to 24 h at room temperature. The method was validated according to International Conference on Harmonization (ICH) guidelines Q2 (R1) Validation of Analytical Procedures. The applicability of the method was tested in a renal pediatric patient. Based on a limited sampling strategy, MPA saliva and plasma concentrations were found in good agreement with each other. We suggest that the described method is suitable to analyze saliva and plasma samples of small volumes for therapeutic drug monitoring (TDM) and pharmacokinetic studies in pediatric patients.
► We present a method to simultaneously quantify MPA and MPAG in saliva and plasma.
► A collection device allowed standardized saliva collection and processing.
► The method appears easy to utilize for pharmacokinetic studies in pediatric patients.
► A non-invasive approach to monitor MPA exposure can be derived from this study.
Journal: Journal of Chromatography A - Volume 1241, 8 June 2012, Pages 52–59