Determination of gamma-hydroxybutyric acid in dried blood spots using a simple GC-MS method with direct 'on spot' derivatization

The objective of this study was the development of an accurate and sensitive method for the determination of gamma-hydroxybutyric acid (GHB) in dried whole blood samples using a GC-MS method. The complete procedure was optimized, with special attention for the sample pre-treatment, and validated. Therefore, dried blood spots (DBS) of only 50 µl were prepared and, after addition of internal standard GHB-d6, directly derivatized using 100 µl of a freshly prepared mixture of trifluoroacetic acid anhydride (TFAA) and heptafluorobutanol (HFB-OH) (2:1). The derivatized extract was injected into a gas chromatograph coupled to a mass spectrometer (GC-MS), operating in the electron impact mode (EI), with a total run time of 12.3 min. Method validation included the evaluation of linearity, precision, accuracy, sensitivity, selectivity and stability. A weighting factor of 1/x2 was chosen and acceptable intra-batch precision, inter-batch precision and accuracy were seen. The linear calibration curve ranged from 2 to 100 µg/ml, with a limit of detection of 1 µg/ml. Our procedure, utilizing the novel approach of direct “on spot” derivatization, followed by analysis with GC-MS, proved to be reliable, fast and applicable in routine toxicology

Feasibility of following up gamma-hydroxybutyric acid concentrations in sodium oxybate (Xyrem®)-treated narcoleptic patients using dried blood spot sampling at home : an exploratory study

Background: Gamma-hydroxybutyric acid (GHB), well known as a party drug, especially in Europe, is also legally used (sodium oxybate, Xyrem (R)) 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 twofold: 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 Respiratory Diseases of Ghent University Hospital were asked to collect DBS approximately 20 min after the first sodium oxybate (Xyrem (R); 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 started 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

Dried blood spots in toxicology : from the cradle to the grave?

About a century after its first described application by Ivar Bang, the potential of sampling via dried blood spots (DBS) as an alternative for classical venous blood sampling is increasingly recognized. Perhaps best known is the use of DBS in newborn screening programs, ignited by the hallmark paper by Guthrie and Susi half a century ago. However, it is only recently that both academia and industry have recognized the many advantages that DBS sampling may offer for bioanalytical purposes, as reflected by the strong increase in published reports during the last few years. Currently, major DBS applications include newborn screening for metabolic disorders, epidemiological surveys (e. g. HIV monitoring), therapeutic drug monitoring (TDM), as well as toxicology. In this review, we provide a comprehensive overview of the distinct subdisciplines of toxicology for which DBS sampling has been applied. DBS sampling for toxicological evaluation has been performed from birth until autopsy, aiming at the assessment of therapeutic drugs, drugs of abuse, environmental contaminants, toxins, as well as (trace) elements, with applications situated in fields as toxicokinetics, epidemiology and environmental and forensic toxicology. We discuss the strengths and limitations of DBS in the different subdisciplines and provide future prospects for the use of this promising sampling technique in toxicology

Energy efficiency analysis of next-generation passive optical network (NG-PON) technologies in a major city network

Ever-increasing bandwidth demands associated with mobile backhaul, content-rich services and the convergence of residential and business access will drive the need for next-generation passive optical networks (NG-PONs) in the long term. At the same time, there is a growing interest in reducing the energy consumption and the associated cost of the access network. In this paper, we consider a deployment scenario in a major city to assess the energy efficiency of various PON solutions from a telecom operator's perspective. We compare five next-generation technologies to a baseline GPON deployment offering similar bandwidths and Quality of Service (QoS) for best-effort high speed connectivity services. We follow two approaches:first, we consider a fixed split ratio (1:64) in an existing Optical Distribution Network (ODN); next, we consider an upgraded ODN with an optimized split ratio for the specific bandwidth and QoS values. For medium bandwidth demands, our results show that legacy PONs can be upgraded to 10G PON without any ODN modification. For future applications that may require access rates up to 1 Gb/s, NG-PON2 technologies with higher split ratios and increased reach become more interesting systems, offering the potential for both increased energy efficiency and node consolidation