Feasibility of Following up Gamma-Hydroxybutyric Acid Concentrations in Sodium Oxybate (Xyrem®)-Treated Narcoleptic Patients Using Dried Blood Spot Sampling at Home

Abstract

Background: Gamma-hydroxybutyric acid (GHB), well known as a party drug, especially in Europe, is also legally used (sodium oxybate, Xyrem ® ) to treat a rare sleep disorder, narcolepsy with cataplexy. This exploratory study was set up to measure GHB concentrations in dried blood spots (DBS) collected by narcoleptic patients treated with sodium oxybate. Intra-and inter-individual variation in clinical effects following sodium oxybate administration has been reported. The use of DBS as a sampling technique, which is stated to be easy and convenient, may provide a better insight into GHB concentrations following sodium oxybate intake in a real-life setting. Objective:The aim was two-fold: evaluation of the applicability of a recently developed DBS-based gas chromatography-mass spectrometry (GC-MS) method, and of the feasibility of the sampling technique in an ambulant setting. Methods: Seven narcoleptic patients being treated with sodium oxybate at the Department for RespiratoryDiseases of Ghent University Hospital were asked to collect DBS approximately 20 min after the first sodium oxybate (Xyrem ® ; UCB Pharma Ltd, Brussels, Belgium) intake on a maximum of 7 consecutive days. Using an automatic lancet, patients pricked their fingertip and, after wiping off the first drop of blood, subsequent drops were collected on a DBS card. The DBS cards were sent to the laboratory by regular mail and, before analysis, were visually inspected to record DBS quality (large enough, symmetrically spread on the filter paper with even colouration on both sides of the filter paper). Results:Of the seven patients, three patients succeeded to collect five series of DBS, one patient decided to cease participation because of nausea, one was lost during follow-up and two patients stated falling asleep almost immediately after the intake of sodium oxybate. Analysing the DBS in duplicate resulted in acceptable within-DBS card precision. DBS with acceptable quality were obtained by patients without supervision. Conclusion:Our results demonstrate the acceptable precision of the complete procedure, from sampling at home to quantitative analysis in the laboratory. Given the intra-and inter-individual variability in clinical effects seen with sodium oxybate, the easy adaptation of DBS sampling opens the possibility of following up GHB concentrations in patients in real-life settings in future studies.3

Opening the toolbox of alternative sampling strategies in clinical routine: A key-role for (LC-)MS/MS

“…To maximize the amount of acceptable spots in the event of home sampling, patient education via demonstration folders and movies has proven to be essential. To evaluate whether contamination occurred during sample collection, incurred sample reanalysis or analysis of a blank filter paper area close to the DBS has been advocated 6,133 . Also for other matrices which are usable for home monitoring, evaluation of sample quality is essential.…”

Alternative Sampling Strategies for Cytochrome P450 Phenotyping

“…Sample collection can be performed by an informed patient himself, eliminating the need for a trained phlebotomist and enabling sampling in a non-specialized environment (e.g. at home) [23]. Furthermore, as several compounds showed enhanced stability in DBS [24][25][26][27], samples can be transferred via regular mail and stored at room temperature in the laboratory.…”

Development and validation of volumetric absorptive microsampling coupled with UHPLC–MS/MS for the analysis of gamma‐hydroxybutyric acid in human blood

“…At-home monitoring of GHB morning plasma concentrations in patients complaining of these side effects could be useful to disclose potential underlying pharmacokinetic mechanisms and optimize the individual dosing schedule. Various methods have been published on the determination of GHB in blood samples both by liquid chromatography-tandem mass spectrometry (LC-MS/MS) (Busardò & Jones, 2015;Dahl, Olsen, & Strand, 2012) and gas chromatography-mass spectrometry (GC-MS) procedures (Ingels, Hertegonne, Lambert, & Stove, 2013;Sadones et al, 2015). In particular, dried blood spot (DBS) has been preliminarily reported as a reliable alternative for classic venous sampling for GHB determination (Forni, Pearl, Gibson, Yu, & Sweetman, 2013;Ingels et al, 2013;Sadones et al, 2015;Saracino et al, 2015).…”