Gas chromatography–electron ionization–mass spectrometry quantitation of valproic acid and gabapentin, using dried plasma spots, for therapeutic drug monitoring in in‐home medical care

Abstract

A simple and sensitive gas chromatography-electron ionization-mass spectrometry (GC-EI-MS) method using dried plasma spot testing cards was developed for determination of valproic acid and gabapentin concentrations in human plasma from patients receiving in-home medical care. We have proposed that a simple, easy and dry sampling method is suitable for in-home medical patients for therapeutic drug monitoring. Therefore, in the present study, we used recently developed commercially available easy handling cards: Whatman FTA DMPK-A and Bond Elut DMS. In-home medical care patients can collect plasma using these simple kits. The spots of plasma on the cards were extracted into methanol and then evaporated to dryness. The residues were trimethylsilylated using N-methyl-N-trimethylsilyltrifluoroacetamide. For GC-EI-MS analysis, the calibration curves on both cards were linear from 10 to 200 µg/mL for valproic acid, and from 0.5 to 10 µg/mL for gabapentin. Intra- and interday precisions in plasma were both ≤13.0% (coefficient of variation), and the accuracy was between 87.9 and 112% for both cards within the calibration curves. The limits of quantification were 10 µg/mL for valproic acid and 0.5 µg/mL for gabapentin on both cards. We believe that the present method will be useful for in-home medical care.

Development and clinical applications of the dried blood spot method for therapeutic drug monitoring of anti‐epileptic drugs

“…DBS cards have been compared in studies on HIV virus load; in contrast, only a few studies on AEDs have been conducted . Ikeda et al compared Whatman FTA DMPK‐A® and Bond Elut DMS® using valproic acid and gabapentin. Both cards demonstrated acceptable precision and accuracy, with DPS ranges of 10‐200 μg/mL for valproic acid and 0.5‐10 μg/mL for gabapentin (calibration curve r 2 > 0.99).…”

“…However, this could only be applied in participants with an Hct level of 30%‐49% . One interesting study of gabapentin by Ikeda et al compared outcomes using Whatman® FTA DMPK‐A® and Bond Elut DMS® paper; both demonstrated acceptable precision and accuracy using the DPS method, which ranged from 0.5 to 10 μg/mL (calibration curve r 2 > 0.99). However, the sample was unstable at 30°C; therefore, storage conditions below this temperature would enable the clinical application of gabapentin.…”

An Updated Overview on Therapeutic Drug Monitoring of Recent Antiepileptic Drugs

“…Therapeutic concentrations of gabapentin in treatment-refractory patients with partial seizures range from 2 to 20 mg/l [55]. HPLC [58], LC/MS-coupled GC [172], and GC-electron ionization-MS [173] methods have been used to quantify serum gabapentin.…”

A validated method for the quantification of fosfomycin on dried plasma spots by HPLC–MS/MS: Application to a pilot pharmacokinetic study in humans

“…Quantification of drugs using the dried plasma spot sampling technique has been described for daptomycin [10], valproic acid and gabapentin [11,12], linezolid [13], paroxetine [14], acetaminophen [15], guanfacine [16], iothalamate [17], vigabatrin [18], triazoles [19], and antiepileptic drugs [20], as well as anti-HIV drugs [21].…”