André Scholer

An automated screening method for drugs and toxic compounds in human serum and urine using liquid chromatography-tandem mass spectrometry

A fully automated screening using liquid chromatography-mass spectrometric method applying data-dependent acquisition was developed to identify toxicologically relevant substances in serum and urine. A library including more than 405 spectra of about 365 compounds (main drugs and important metabolites) was established. An easy to use program was created to automate and accelerate library search. Drugs were identified based on their relative retention times, molecular ions and fragment ions. Limits of detection were tested with 100 of the 365 compounds the majority of these were lower than 100μg/l (67%). The developed LC-MS-MS system seems to be a valuable alternative to other general unknown screening methods allowing fast and specific identification of drugs in serum and urine samples.

High prevalence of unknown co-medication in hospitalised patients.

ObjectiveCo-medication unknown to the treating physician, including self-medication, may compromise drug safety by increasing the risk of duplicate therapy, drug interactions and adverse drug reactions that are not recognised as such. The aim of the current study was to estimate exposure to unknown co-medication during hospitalisation by performing an analytical screening for a broad range of drugs and drug classes in urine of patients admitted to a general internal medicine ward.MethodsUrine samples of 44 patients were analysed with REMEDiHS (high-performance liquid chromatography) and six different immunoassays. Positive results were compared with drug history and documented drug prescription. If appropriate, gas chromatographic-mass spectrometric confirmatory analyses were performed on drugs classified at least once as possible unknown co-medication.ResultsNine (20%) of the patients tested positive for a compound detected by two independent analytical methods and 18 (41%) for a compound detected by at least one analytical method. Unknown co-medication consisted mostly of analgesics, benzodiazepines or ranitidine.ConclusionAt least one in five patients exhibits at least once during hospitalisation exposure to drugs not documented in the patient record, which may compromise patient safety.

An enzymatic method to determine γ-hydroxybutyric acid in serum and urine.

Background: Gamma-hydroxybutyric acid (GHB) has become one of the most dangerous illicit drugs of abuse today. It is used as a recreational and date rape drug because of its depressant effect on the central nervous system, which may cause euphoria, amnesia, respiratory arrest, and coma. There is an urgent need for a simple, easy-to-use assay for GHB determination in urine and blood. In this article, a rapid enzymatic assay adapted to clinical chemistry analyzers for the detection of GHB is presented. Methods: The described GHB enzymatic assay is based on a recombinant GHB dehydrogenase. The full validation of the assay was performed on a Konelab 30 analyzer (Thermo Fisher Scientific). Results: The analytical sensitivity was <1.5 mg/L, whereas the functional sensitivity was 4.5 mg/L in serum and 2.8 mg/L in urine. The total imprecision coefficient of variation (CV) was <9.8% in serum and <7.9% in urine. The within-run imprecision showed a CV of <3.8% in serum and <4.6% in urine. The assay was linear within the range 5–250 mg/L. Mean recoveries were 109% in serum and 105% in urine. No cross-reactivity was observed for tested GHB analogues and precursors. Comparison of GHB-positive samples showed an excellent correlation with ion chromatography, gas chromatography–mass spectrometry, and liquid chromatography associated to tandem mass spectrometry. Except for ethanol, no substantial interference from serum constituents and some drugs was observed. Conclusions: This automated GHB assay is fully quantitative and allows the accurate measurement of GHB in serum and urine. It can be used as a rapid screening assay for the determination of GHB in intoxicated or overdosed patients.

Sensitivity and specificity of urinary cannabinoid detection with two immunoassays after controlled oral administration of cannabinoids to humans

For forensic and clinical toxicologic purposes, cannabis consumption is screened using easy-to-handle immunoassays. The sensitivity and specificity of these immunoassays have not yet been established in samples from volunteers receiving oral synthetic tetrahydrocannabinol or cannabis extracts using liquid chromatography-mass spectrometry/mass spectrometry as the reference method. Urine samples were collected in an open, randomized, single-center, three-period crossover study including 18 healthy male volunteers given either 20 mg synthetic tetrahydrocannabinol (Marinol) as a control substance or five different types of Cannabis sativa extracts.