Volumetric absorptive microsampling as an alternative tool for therapeutic drug monitoring of first-generation anti-epileptic drugs

Abstract

Dosage adjustment of anti-epileptic drugs by therapeutic drug monitoring (TDM) is very useful, especially for the first-generation anti-epileptic drugs (AEDs). Microsampling-the collection of small volumes of blood-is increasingly considered a valuable alternative to conventional venous sampling for TDM. Volumetric absorptive microsampling (VAMS) allows accurate and precise collection of a fixed volume of blood, eliminating the volumetric blood hematocrit bias coupled to conventional dried blood spot collection. The aim of this study was to develop and validate an LC-MS/MS method for the determination and quantification of four anti-epileptic drugs (carbamazepine, valproic acid, phenobarbital, and phenytoin) and one active metabolite (carbamazepine-10,11-epoxide) in samples collected by VAMS. The method was fully validated based on international guidelines. Precision (%RSD) was below 10%, while, with a single exception, accuracy (%bias) met the acceptance criteria. Neither carry-over nor unacceptable interferences were observed, the method being able to distinguish between the isomers oxcarbazepine and carbamazepine-10,11-epoxide. All compounds were stable in VAMS samples for at least 1 month when stored at room temperature, 4 °C, and - 20 °C and for at least 1 week when stored at 60 °C. Internal standard-corrected matrix effects were below 10%, with %RSDs below 4%. High (> 85%) recovery values were obtained and the effect of the hematocrit on the recovery was overall limited. Successful application on external quality control materials and on left-over patient samples demonstrated the validity and applicability of the developed procedure. Graphical abstract Graphical representation of the sampling, chemical structures, and the resulting chromatogram for volumetric absorptive microsampling (VAMS)-based therapeutic drug monitoring of first-generation anti-epileptic drugs by liquid chromatography with tandem mass spectrometric detection.

Determination of iohexol by capillary blood microsampling and UHPLC-MS/MS

“…Itraconazole was analyzed from VAMS as low soluble molecule model [19]. For therapeutic drug monitoring, the first-generation anti-epileptic drugs and hydrochloroquine were determined using VAMS samples [20,21]. Even asenapine enantiomers have been quantified from VAMS samples using an LC-Diode array detector platform [22].…”

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

“…Differently from the findings from Moorthy et. al., in our cohort, the concentration of CBD obtained from capillary blood sampled by VAMS did not differ from those obtained from venous blood and plasma [37,39,40]. This may be due to the different approach used as we employed real samples obtained from patients to which CBD was administered in a clinical setting, while the comparison of Moorthy et.…”

“…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 ].…”

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).…”