Dried Blood Spot Punches for Confirmation of Suspected γ-Hydroxybutyric Acid Intoxications: Validation of an Optimized GC–MS Procedure

Ingels, Ann-Sofie; Paepe, Peter De; Anseeuw, Kurt; Sassenbroeck, Diederik Van; Neels, Hugo; Lambert, Willy E.; Stove, Christophe

doi:10.4155/bio.11.204

Cited by 44 publications

(42 citation statements)

References 28 publications

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“…Hct and blood volume had a considerable impact on the concentrations of caffeine and paraxanthine, similar to that described for several other small molecules [32][33][34][35]. The range in which the impact of Hct was evaluated, 0.20 -0.60, was considered to be relevant and sufficient, as it covers approximately 99.5% of a hospital population (including both 'normal' and 'critically ill' patients) [10].…”

Section: Discussionmentioning

confidence: 92%

Why Dried Blood Spots Are an Ideal Tool for CYP1A2 Phenotyping

2014

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Background and ObjectiveDried blood spot (DBS) sampling has gained wide interest in bioanalysis during the last decade. Also in pharmacokinetic and phenotyping studies, DBS-based sampling has already been successfully applied. However, all available phenotyping studies used small data sets and did not include a systematic evaluation of DBS-specific parameters. The latter is important since several of these factors still challenge the breakthrough of DBS in routine practice. In this study, caffeine and paraxanthine are determined in capillary DBS, venous DBS, whole blood and plasma for CYP1A2 phenotyping (CYP; cytochrome P450). The aim of this study was to explore the usefulness of DBS as a tool for CYP1A2 phenotyping. MethodsA CYP1A2 phenotyping study was conducted in seventy-three healthy volunteers, who received a 150 mg oral dose of caffeine. Six hours post-administration, caffeine and paraxanthine concentrations and paraxanthine:caffeine molar concentration ratios, i.e. the actual CYP1A2 phenotyping indices, were determined in capillary DBS (obtained by non-volumetric application, direct from the fingertip), venous DBS, whole blood and plasma. Furthermore, the impact of DBS-specific parameters, including hematocrit, volume spotted and punch location, was evaluated. ResultsConcentrations of caffeine and paraxanthine in capillary DBS were on average 12.7 respectively 13.8 % lower than those in venous DBS and 31.5 respectively 33.1 % lower than those in plasma. While these differences were statistically significant (p < 0.001), no significant difference was observed between the paraxanthine:caffeine molar ratios in the distinct evaluated matrices (p ≥ 0.053). This ratio also alleviated the impact of hematocrit and volume spotted. ConclusionsUsing the largest DBS-based phenotyping study to date, we have demonstrated that CYP1A2 phenotyping in capillary DBS is a valid and convenient alternative for the classical plasma-based approach. Additionally, we have provided an objective basis as to why DBS are an ideal tool for CYP1A2 phenotyping.  While capillary DBS concentrations of caffeine and paraxanthine differed significantly from those in venous blood and plasma and were impacted by hematocrit and blood volume spotted, the paraxanthine:caffeine molar ratio essentially remained unaffected. Capillary DBS-based CYP1A2 phenotyping proved to be a valid and convenient alternative for the classical plasma-based approach.4

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Section: Discussionmentioning

confidence: 92%

Why Dried Blood Spots Are an Ideal Tool for CYP1A2 Phenotyping

2014

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“…Based on that study, it can be concluded that DBS from capillary blood can be used as a suitable alternative for venous blood. [7] 3 Results…”

Section: Dbs Analysismentioning

confidence: 99%

“…One µL of the derivatized extract was injected into the GC-MS, operating in selective ion monitoring (SIM) mode for quantification. [7] The method used has a lower and upper limit of quantification of 2 and 100 µg/mL GHB, respectively. Of those DBS with a GHB concentration above 100 µg/mL, the final ethylacetate extracts were diluted ten-fold according to the previously validated dilution technique.…”

Section: Dbs Analysismentioning

confidence: 99%

“…While the first drop was wiped off with a sterile piece of cloth because of the presence of tissue fluid, the subsequent drops were collected on the DBS card. [7] After overnight drying (horizontal on a clean and empty glass), the card was placed in a zip-closure plastic bag and, finally, all the cards were sent to the laboratory by regular mail.…”

Section: Dried Blood Spots (Dbs) Collectionmentioning

confidence: 99%

“…The first objective was to evaluate the applicability of a recently developed and validated DBS-based gas chromatography-mass spectrometry (GC-MS) method. [7] Whereas DBS sampling has been used for decades in newborn screening, more recently, this alternative sampling strategy is increasingly gaining interest in the context of therapeutic drug monitoring, (pre-) clinical studies and toxicology. Having advantages such as being easy to perform and minimally invasive, DBS sampling renders blood sampling by the patient at home a feasible option, allowing better insight to be gained into GHB concentrations following sodium oxybate administration.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2013

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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

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Beyond Dried Blood Spots—Application of Dried Matrix Spots

Needham¹

2014

Dried Blood Spots

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Dried Blood Spot Punches for Confirmation of Suspected γ-Hydroxybutyric Acid Intoxications: Validation of an Optimized GC–MS Procedure

Abstract: A sensitive GC-MS method for GHB analysis in DBS was successfully optimized and validated. The successful analysis of DBS collected from GHB abusers suggests the routine applicability of the DBS sampling technique for GHB analysis in toxicological cases.

Cited by 44 publications

References 28 publications

Why Dried Blood Spots Are an Ideal Tool for CYP1A2 Phenotyping

Why Dried Blood Spots Are an Ideal Tool for CYP1A2 Phenotyping

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

Beyond Dried Blood Spots—Application of Dried Matrix Spots

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