Volumetric Absorptive Microsampling: A New Sampling Tool for Therapeutic Drug Monitoring of Antiepileptic Drugs

Abstract

Background: Volumetric absorptive microsampling (VAMS) is a novel sampling technique for the collection of fixed-volume capillary blood. In this study, a new analytical method was developed and used to quantify 14 different antiepileptic drugs (AEDs) and 2 active metabolites in samples collected by VAMS. These data were compared with concentration measurements in plasma. Methods: The authors developed a selective and sensitive liquid chromatography–mass spectrometry (LC-MS/MS) assay to measure the concentrations of several AEDs in whole blood collected by VAMS, which were compared with a commercially available LC-MS/MS kit for AED monitoring in plasma. Drugs and internal standards were extracted from whole blood/plasma samples by a simple protein precipitation. Results: An LC-MS/MS method analyzing VAMS samples was successfully developed and validated for the determination of various AED concentrations in whole blood according to EMA guidelines for bioanalytical method validation. Extraction recovery was between 91% and 110%. No matrix effect was found. The method was linear for all drugs with R2 ≥0.989 in all cases. Intra-assay and inter-assay reproducibility analyses demonstrated accuracy and precision within acceptance criteria. Carry over and interferences were negligible. No volumetric HCT% bias was found at 3 different HCT values (35%–55%) with recovery being consistently above 87%. Samples are very stable at temperatures ranging from −20°C to 37°C and for a 4-month period. Leftover EDTA samples from 133 patients were tested to determine concentration differences between plasma and whole blood sampled by VAMS. The resulting difference varied less than 15% apart from those drugs with a blood/plasma ratio (R) different from 1. Conclusions: The assay allows for highly sensitive and selective quantification of several AEDs in whole blood samples collected by VAMS. The developed method is accurate and precise and free from matrix effects and volumetric HCT% bias.

Blood and Plasma Volumetric Absorptive Microsampling (VAMS) Coupled to LC-MS/MS for the Forensic Assessment of Cocaine Consumption

“…The first step of the study was the testing of VAMS volume accuracy for plasma sampling, followed by the development of a suitable pretreatment procedure. Blood volume accuracy was taken for granted, according to the results of previous reports [38][39][40].…”

Cannabidiol Determination on Peripheral Capillary Blood Using a Microsampling Method and Ultra-High-Performance Liquid Chromatography Tandem Mass Spectrometry with On-Line Sample Preparation

“…These systems allow to collect a known volume of blood by means of microfluidic system, nullifying the HCT and drop volume effects on the analytes determination [17,[19][20][21]. Herein, we describe a new microsampling method for the simultaneous determination of THC and CBD using VAMS which has been demonstrated useful for the quantitative measurement of several drugs from venous and capillary blood including first-generation and third-generation antiseizure drugs [23,37], antibiotics [22] and immunosuppressants [35][36][37].…”

“…Compared to the classical non-volumetric-based dried blood spots (DBS) analysis, the performances of this device are not influenced by the hematocrit (HCT) values and by the erythrocyte volume fraction [17][18][19][20][21]. VAMS approach has been yet adopted for several quantitative methods for several molecules in different fields [19,22,23].…”

A Volumetric Absorptive Microsampling Technique to Monitor Cannabidiol Levels in Epilepsy Patients

“…However, to date, the TDM of medical cannabis has few validated analytical methods on plasma (Grauwiler et al, 2007;Aizpurua-Olaizola et al, 2017;Lomonaco et al, 2018;Pigliasco et al, 2020). We used a new microsampling method for the determination of CBD blood levels in patients with drug-resistant epilepsy using VAMS, which had previously proven useful for quantitative measurement of several venous and capillary blood drugs, including first and third-generation antiepileptic drugs (Velghe and Stove, 2018;DʼUrso et al, 2019), antibiotics (Barco et al, 2017) and immunosuppressants (Koster et al, 2019).…”

“…Recently, the novel device VAMS (Volumetric Absorptive Microsampling) has been introduced in the market, commercial name MITRA®, successfully applied to several quantitative TDM methods. This device allows the collection of a fixed volume of blood (10 or 30 µl) avoiding the effect of hematocrit (HCT) on the analytical performances (Mano et al, 2015;Barco et al, 2017;Kok and Fillet, 2018;DʼUrso et al, 2019). We evaluated VAMS in combination with liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) for the quantification of CBD blood levels to be used in clinical practice to personalize the cannabis-based treatment of refractory epilepsy.…”