Application of Direct Urine LC-MS-MS Analysis for Screening of Novel Substances in Drug Abusers

Abstract

A newly developed liquid chromatography-tandem mass spectrometry (LC-MS-MS) method was used to study 3000 human urine samples from 3 different populations for 23 analytes covering phenylethylamines, benzylpiperazine, and non-benzodiazepine hypnotics. Direct injection of urine and LC-MS-MS with rapid chromatography and atmospheric pressure chemical ionization was used in the screening step. The cutoff levels were chosen to be at the limit of detection for most analytes to identify as many positive samples as possible. Typically one ion transition was monitored from the pseudo-molecular ions in the multiple reaction monitoring mode. Of the 797 positive screening findings, 518 (65%) were confirmed by a second LC-MS-MS analysis including solid-phase extraction. Confirmed analytical findings included 22 cases positive for N-benzylpiperazine, 88 for 3,4-methylenedioxy-N-methylamphetamine and metabolites, 4 for 1-phenyl-2-butylamine, 24 for zolpidem and metabolites, 118 for zopiclone and metabolites, and 1 for zaleplon. In conclusion, LC-MS-MS was found to be a robust alternative for drugs of abuse screening, offering high sensitivity compared with immunochemical screening methodology.

HPLC–ESI-MS/MS validated method for simultaneous quantification of zopiclone and its metabolites, N-desmethyl zopiclone and zopiclone-N-oxide in human plasma

“…As hypnotics and benzodiazepines are routinely screened for clinical and forensic toxicology applications, several analytical procedures are reported to determine zopiclone and/or its metabolites in a variety of biological matrices like, whole blood [6][7][8][9][10], plasma [11][12][13][14][15][16][17][18][19][20][21][22][23], serum [10,[24][25][26][27], urine [7,10,14,23,[28][29][30][31][32][33][34][35][36], hairs [7,37], nails [37], oral fluids [38,39] and others [40]. These methods have been developed employing different analytical techniques viz.…”

“…These methods have been developed employing different analytical techniques viz. capillary electrophoresis [28], radioimmunoassay [33,35], gas chromatography [8,11,15,20,27], gas chromatography-mass spectrometry [6,8,30,40], liquid chromatography-mass spectrometry [7,10,17,24,29,31,[37][38][39], high performance liquid chromatography with UV [9,13,18,19,22,25,32], diode array [21,40] and fluorescence detection [10,12,14,16,36]. Majority of these methods are for the detection and quantitation of zopiclone in combination with other benzodiazepines.…”

Screening for basic drugs in equine urine using direct-injection differential-gradient LC–LC coupled to hybrid tandem MS/MS

“…We adopted a direct injection LC-MS/MS set-up when developing a new screening method aimed at detecting a wide variety of drugs in equine urine, as this had previously been shown to be successful [7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23].…”

Quantitative determination of total methamphetamine and active metabolites in rat tissue by liquid chromatography with tandem mass spectrometric detection

“…A review of the recent literature indicates that on-line or off-line solid-phase extraction (SPE) before analytical separation is by far the most popular means of sample preparation prior to MS/MS. [30][31][32][33][34][35][36][37][38][39][40] Liquid-liquid extraction (LLE) has been touted as advantageous over SPE because the purity of the solvents used is easier to control when compared with potential impurities in SPE materials. Despite this advantage, LLE is not a popular means of biological sample preparation as shown by a search of recent literature.…”