High Throughput Detection of 327 Drugs in Blood by LC–MS-MS with Automated Data Processing

Abstract

The described procedure provides a rapid technique for the detection and semi-quantitation of a large number of drugs in blood. This procedure uses a minimal sample volume and employs a one-step liquid extraction and automated data processing to yield rapid turnaround times. 327 of the most commonly used medicinal and illicit drugs in Australia were selected including various amphetamines, anesthetics, anti-depressants, anti-psychotics, anti-convulsants, benzodiazepines, beta blockers, opioid and non-opioid analgesics, stimulants, THC and a large number of synthetic cannabinoids and other novel psychoactive substances. The extracts were subject to 5-minute chromatography using a Kinetex C18 50 x 4.6 mm 2.6 μm solid-core analytical column and analyzed using a Sciex 3200 Q-TRAP MS-MS (+ ESI, MRM mode, two transitions per analyte). The method was fully validated in accordance with international guidelines. Matrix effects and extraction efficiencies were acceptable with most analytes showing > 80% response and low variation (within 25%RSD). Cannabinoids were most affected by the matrix and yielded poorest recovery values but were still detectable. Precision, accuracy, repeatability and multipoint linearity were assessed for all analytes. The method has been used in routine practice in the forensic toxicology service at the Victorian Institute of Forensic Medicine in over 6000 coronial investigations using both post-mortem and clinical blood specimens. This technique has greatly increased throughput, reduced turnaround times and allowed for rapid same-day analysis of results when needed. The method is routinely used in routine overnight testing with results reported to pathologists within 4 hours of data acquisition. This rapid toxicological technique is used in conjunction with other investigative processes such as full-body CT imaging, review of case circumstances and medical histories to provide an efficient death investigation process.

Early Warning System for Illicit Drug Use at Large Public Events: Trace Residue Analysis of Discarded Drug Packaging Samples

“…In contrast, mass spectrometry (MS) is widely acknowledged as the gold standard analytical measurement technology for forensic drug analysis, including for drug monitoring. , MS, when coupled with established chromatographic separation techniques, namely, gas chromatography (GC)-MS and liquid chromatography (LC)- electrospray ionization (ESI)-MS or tandem mass spectrometry (MS/MS), − is capable of providing definitive qualitative and quantitative drug identifications with high sensitivity and specificity, including for low-level components within polydrug mixtures, by matching the observed retention times, mass-to-charge ratios, and/or characteristic fragmentation patterns for each drug against information contained within reference libraries generated from authentic standards. , MS techniques are also capable of de novo identification and characterization of novel drug substances that appear on the market.…”

Postmortem Metabolomics: Strategies to Assess Time-Dependent Postmortem Changes of Diazepam, Nordiazepam, Morphine, Codeine, Mirtazapine and Citalopram

“…In order to exclude a significant influence of the storage conditions and/or shipment on the presented study, quantification results of 90 randomly selected cases were compared in a first step. The selected reference points were the drug concentrations of diazepam, nordiazepam, morphine, codeine, mirtazapine and citalopram obtained during routine analysis at the Victorian Institute of Forensic Medicine (VIFM) for mortuary admission samples (t1) utilizing a high throughput method for semi-quantification of 327 drugs in blood [ 18 ]. These were compared to quantification results at the Zurich Institute of Forensic Medicine (ZIFM) after storage and shipment as detailed in the materials and methods section [ 19 ].…”

Diclofenac Concentrations in Post-Mortem Specimens—Distribution, Case Reports, and Validated Method (UHPLC-QqQ-MS/MS) for Its Determination

“…In four articles [ 58 , 61 , 64 , 66 ] an isotope-labeled standard of diclofenac has been used as the internal standard. The most popular method of sample preparation was protein precipitation [ 59 , 60 , 61 , 65 , 68 , 69 ] followed by liquid–liquid extraction (LLE) [ 58 , 64 , 66 , 70 ]. The most sensitive method (LOQ: 0.05 ng/mL) was developed by Nazario and Lancas [ 58 ]; however, the authors used two steps for LLE, which is complicated and time-consuming.…”