euro-toxicology-2016_scientifictracks-abstracts

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Volume 6, Issue 6(Suppl) J Clin Toxicol 2016
ISSN: 2161-0495, JCT an open access journal
Page 44
Notes:
Euro Toxicology 2016
October 24-26, 2016
conferenceseries.com
Toxicology & Applied Pharmacology
October 24-26, 2016 Rome, Italy
7th Euro-Global Summit on
Targeted screening of succinic semialdehyde dehydrogenase deficiency (SSADHD) employing an
enzymatic assay for γ-hydroxybutyric acid (GHB) in biofluids
Cédric Wernli
University of Applied Science and Arts, Switzerland
Introduction: An enzymatic assay for quantification of γ-hydroxybutyric acid (GHB) in biofluids can be employed for targeted
screening of succinic semialdehyde dehydrogenase deficiency (SSADHD) in selected populations. We used a two-tiered study
approach, in which the first study (proof of concept) examined seven urine samples derived from patients with SSADHD and
five controls, and the second study (feasibility study) examined a broader sample population of patients and controls, including
plasma.
Objective: Aim of this study was to evaluate split samples of urine and plasma (anonymized) by enzymatic assay, gas
chromatography alone (proof of concept) and gas chromatography-mass spectrometry, and the results compared.
Method: Multiple detection methods have been developed to detect GHB. We evaluated an enzymatic assay which employs
recombinant GHB dehydrogenase coupled to NADH production, the latter quantified on a Cobas Integra 400 Plus.
Results: In our proof of concept study, we analyzed 12 urine samples (five controls, seven SSADHD) and in the feasibility study,
we evaluated 33 urine samples (23 controls, 10 SSADHD) and 31 plasma samples (14 controls, 17 SSADHD). The enzymatic
assay carried out on a routine clinical chemistry analyzer was robust, revealing excellent agreement with instrumental methods
in urine (GC-FID: r=0.997, p ≤ 0.001; GC-MS: r=0.99, p≤ 0.001); however, the assay slightly over-estimated GHB levels in
plasma, especially those in which GHB levels were low. Conversely, correlations for the enzymatic assay with comparator
methods for higher plasma GHB levels were excellent (GC-MS; r=0.993, p≤ 0.001).
Conclusion: We have evaluated the capacity of this enzymatic assay to identify patients with SSADHD via quantitation of GHB.
The data suggests that the enzymatic assay may be a suitable screening method to detect SSADHD in selected populations
using urine. In addition, the assay can be used in basic research to elucidate the mechanism of the underlying disease or
monitor GHB-levels for the evaluation of drug candidates.
Biography
Cédric Wernli worked for about 10 years as a Lab Technician in the Clinical Chemistry laboratory in Toxicology department at the University Hospital in Basel. After
his studies in Pharmacy at University of Basel (MSc in Pharmacy, 2013), he passed the board exam as a Pharmacist in October 2013. Since then, he works as a
PhD-student at the University of Basel in coorperation with the University of Applied Science and Arts Northwestern Switzerland in developing quantitative lateral
flow immunoassays for therapeutic drug monitoring in whole blood.
Cédric Wernli, J Clin Toxicol 2016, 6:6(Suppl)