Development of a multi‐target screening analysis for 301 drugs using a QTrap liquid chromatography/tandem mass spectrometry system and automated library searching

Abstract

A new multi-target screening (MTS) procedure for drugs in blood and urine for toxicological analysis has been developed using a hybrid triple-quadrupole linear ion trap mass spectrometer (QTrap) for the fast detection and identification of 301 forensically important drugs, e.g. tranquilizers (benzodiazepines), hypnotics, drugs of abuse (opiates, cocaine, amphetamines, cannabinoids), antidepressants, neuroleptics, and some cardiac drugs, in one single liquid chromatography/tandem mass spectrometry (LC/MS/MS) analysis. Samples were extracted either with liquid-liquid extraction or solid-phase extraction. A multiple reaction monitoring (MRM) as survey scan and an enhanced product ion (EPI) scan as dependent scan were performed in an information-dependent acquisition (IDA) experiment. Finally, drug identification was carried out by library search with a newly developed MS/MS library based on EPI spectra at three different collision energies in positive mode. The advantage of this newly developed method is the possibility to detect and identify 301 drugs in one single LC/MS/MS run.

Rapid detection and identification of N-acetyl-L-cysteine thioethers using constant neutral loss and theoretical multiple reaction monitoring combined with enhanced product-ion scans on a linear ion trap mass spectrometer

“…Additional specificity is gained by recording the corresponding characteristic product ion mass spectrum of each signal detected by the MRM scan. This has recently been shown for 301 drugs° [14].…”

“…With a conventional tandem MS, a product ion scan can only be performed in a second chromatographic separation and, in addition, the instrument is less sensitive than ion trap instruments [12,13]. Therefore, the combination of a tandem mass spectrometer and a sensitive ion trap in a single instrument is the instrument of choice for precursor ion scan (PreIS) or CNL combined with the acquisition of product ion mass spectra [14,15].…”

Fast screening of 88 pharmaceutical drugs and metabolites in whole blood by ultrahigh-performance liquid chromatography–tandem mass spectrometry

“…Whenever these analytes are not known in advance or interferents are present, preliminary multi-target screening procedures proved to be necessary before accurate quantification [1]. Screening methods based on immunoassay testing are available only for few classes of drugs [6][7][8]-such as cannabinoids, cocaine, amphetamines, opiates, methadone, benzodiazepines, barbiturates, and tricyclic antidepressants-whereas no immunoassays are commercially available for the newest designer drugs [1] and other common substances, including anesthetics, antihistamines, and sedative-hypnotics [4]. Moreover, the use of multiple immunoassays testing requires a considerable amount of blood samples.…”

Identificação de substâncias em análise toxicológica sistemática utilizando um sistema informatizado para cálculo de parâmetros cromatográficos e busca em bases de dados

“…Apesar da disponibilidade de métodos analíticos modernos de elevada sensibilidade e especificidade, tais como a cromatografia líquida associada à espectrometria de massas em tandem (CL-EM/ EM) 7,8 e espectrometria de massas por tempo de vôo (CL-TDV) 9 , a maior parte dos laboratórios de toxicologia analítica ainda utilizam métodos clássicos, como a cromatografia em camada delgada (CCD), cromatografia gasosa (CG) com detectores não espectrométricos, como os de ionização em chama (DIC) e nitrogênio-fós-foro (DNP), e a cromatografia líquida de alta eficiência com detecção por absorção de radiação ultravioleta (CLAE-UV) 2,5,6 .…”