high-throughput-comprehensive-drug-surveillance-using-multisegment

High-throughput and Comprehensive Drug Surveillance Using Multisegment Injection-Capillary Electrophoresis-Mass Spectrometry

New analytical methods are urgently needed to enable high-throughput, yet comprehensive drug screening, given an alarming opioid and prescription drug ...

Agilent Technologies Inc.

The advantage of using naphthenic acid (NA) mixtures for the determination of total NA lies in their chemical characteristics and identification of retention times distinct from isobaric interferences. However, the differing homolog profiles and unknown chemical structures of NA mixtures do not allow them to be considered a traceable reference material. The current study provides a new tool for the comparative assessment of different NA mixtures by direct reference to a single, well-defined and traceable compound, decanoic-d acid. The method employed an established liquid chromatography time-of-flight mass spectrometry (LC/QToF) procedure that was applicable both to the classic O2 NA species dominating commercial mixtures and additionally to the O4 species known to be present in acid extractable organics (AEOs) derived from oil sands process water (OSPW). Four different commercial NA mixtures and one OSPW-derived AEOs mixture were comparatively assessed. Results showed significant difference among Merichem Technical, Aldrich, Acros, and Kodak commercial NA mixtures with respect to "equivalent to decanoic-d acid" concentration ratios to nominal. Furthermore, different lot numbers of single commercial NA mixtures were found to be inconsistent with respect to their homolog content by percent response. Differences in the observed homolog content varied significantly, particularly at the lower (n = 9-14) and higher (n = 20-23) carbon number ranges. Results highlighted the problem between using NA mixtures from different sources and different lot numbers but offered a solution to the problem from a concentration perspective. It is anticipated that this tool may be utilized in review of historical data in addition to future studies, such as the study of OSPW derived acid extractable organics (AEOs) and fractions employed during toxicological studies.

A traceable reference for direct comparative assessment of total naphthenic acid concentrations in commercial and acid extractable organic mixtures derived from oil sands process water.

New technologies are urgently required for reliable drug screening given a worldwide epidemic of prescription drug abuse and its devastating socioeconomic impacts on public health. Primary screening of drugs of abuse (DoA) currently relies on immunoassays that are prone to bias and are not applicable to detect an alarming array of psychoactive stimulants, tranquilizers, and synthetic opioids. These limitations impact patient safety when monitoring for medication compliance, drug substitution, or misuse/abuse and require follow-up confirmatory testing by more specific yet lower throughput instrumental methods. Herein, we introduce a high throughput platform for nontargeted screening of a broad spectrum of DoA and their metabolites based on multisegment injection-capillary electrophoresis-mass spectrometry (MSI-CE-MS). We demonstrate that MSI-CE-MS enables serial injections of 10 samples within a single run (<3 min/sample) where multiplexed electrophoretic separations are coupled to high resolution MS with full-scan data acquisition. Unambiguous drug identification was achieved by four or more independent parameters, including comigration with a deuterated internal standard or in silico prediction of electromigration behavior together with accurate mass, most likely molecular formula, as well as MS/MS as required for confirmation testing. Acceptable precision was demonstrated for over 50 DoA at 3 concentration levels over 4 days (median coefficient of variance = 13%, n = 117) with minimal ion suppression, isobaric interferences, and sample carry-over (<1%). This approach offers a rapid yet accurate method for simultaneous detection and identification of DoA at their recommended screening cutoff levels in human urine while allowing for systematic surveillance, specimen verification, and retrospective testing of designer drugs that elude conventional drug tests.

High Throughput Screening Method for Systematic Surveillance of Drugs of Abuse by Multisegment Injection-Capillary Electrophoresis-Mass Spectrometry.

A high resolution mass spectrometry method was developed for the environmental impact monitoring of oil spill dispersants. Previously reported instability of dioctyl sulfosuccinate (DOSS) dispersant tracer was addressed by the new procedure. The method monitors both DOSS and its degradation product, monooctyl sulfosuccinate (MOSS), by liquid chromatography time-of-flight mass spectrometry. The related isomer, 4-(2-ethylhexyl) 2-sulfobutanedioate, was chromatographically resolved from MOSS but was not a product of DOSS degradation. Using this direct injection method (10 μL), the practical lower limit of quantitation was 0.5 nM for each analyte, a concentration equivalent to 0.22 ng mL, or 0.30 ng mL including initial dilution factor with acetonitrile. The method was shown applicable to analysis of the dispersants Corexit® EC9500 A, Finasol OSR 52, Slickgone NS, and Slickgone EW for which DOSS is an active ingredient. A marine microcosm study of Corexit EC9500A, together with diluted bitumen (dilbit), at 15 ± 1 °C, provided evidence of the stoichiometric conversion of DOSS to MOSS under conditions reflecting a western Canadian marine environment. The advantage of the developed method is in its ability to extend environmental seawater sample collection time from 4 days for DOSS alone, to 14 days when both DOSS and MOSS are simultaneously analysed and results combined. The collection time is likely extended beyond the 14 day period with cooler temperatures. Preservation of collected seawater samples using sodium hydroxide, converting DOSS into MOSS in situ, was rejected due to stability issues. Addition of disodium ethylenediaminetetraacetic acid did not improve hold times, thus eliminating the theory of cation induced micelle effects causing DOSS loss.

Marcus Kim

Agilent Technologies Inc.

High-throughput and Comprehensive Drug Surveillance Using Multisegment Injection-Capillary Electrophoresis-Mass Spectrometry