General unknown screening

To be able to use MS/MS spectra library searching for general unknown screening, it is necessary to use an automatic process, called data dependent acquisition or information-dependent acquisition, to select the parent ions of interest, totally unexpected by definition, and to dissociate them and monitor their fragments. 

General Unknown Screening of Pharmacologically and Toxicologically Relevant Compounds... 

Marquet, P., N. Venisse, E. Lacassie, et al. 2000. In-source CID mass spectral libraries for the general unknown screening of drugs and toxicants. Analusis 28 925-934. 

Its largest field of application, which will focus on this chapter, is the multiresidual analysis in biological samples. In so-called confirmatory analyses, LC-MS, or better LC-MS/MS, provides an unequivocal identification, due to the high selectivity of the MS detector. The results of Systematic Toxicological Screening Analysis (STA) or General Unknown Screening (GUS), other applications of LC-MS, needs of subsequent confirmatory analysis to be used in a court [52, 55]. 

Marquet, P., Saint-Marcoux, F., Gamble, T.N., Leblanc, J.C. (2003). Comparison of a preliminary procedure for the general unknown screening of drugs and toxic compounds using a quadrupole-linear ion-trap mass spectrometer with a liquid chromatography-mass spectrometry reference technique. J. Chromatogr. B Anal. Technol. Biomed. Life Sci. 789(1) 9-18. 

F. Saint-Marcoux, G. Lachatre, P. Marquet, Evaluation of an improved general unknown screening procedure using LC-ESI-MS by comparison with GC and LC-DAD, J. Am. Soc. Mass Spectrom., 14 (2003) 14. 

Recently, LC-MS techniques have become increasingly popular as an approach to analytical problems. In keeping with this development, Saint-Marcoux et al described a general unknown screening procedure for serum samples, using SPE and subsequent liquid chromatography-electrospray mass spectrometry (LC-ESIMS). This method allows for the detection and identification of pesticides and also other drugs and toxic compounds. 

Saint-Marcoux F, Lachatre G, Marquet P. Evaluation of an improved general unknown screening procedure using liquid chromatography-electrospray-mass spectrometry by comparison with gas chromatography and high-performance liquid chromatography-diode array detection. J Am Soc Mass Spectrom 2003 14 14 22. 

When a sample set has been determined to be statistically representative of the population submitted to the laboratory and homogenised when appropriate, the next step is to determine whether or not an extraction technique, such as liquid-liquid extraction (LLE) or solid phase extraction (SPE) is necessary (see Chapter 3 for explanation of these techniques). If the sample size is large enough and the type of drug substance that may be present is unknown, a series of presumptive tests can be carried out, as can a general unknown screen. 

Presumptive tests are a series of colour tests that can provide an indication as to the class of drugs that might be present however, because these tests are subjective, confirmatory analysis must also be carried out. A general unknown screen is commonly carried out using GC-MS, although EC-MS has also recently found an application in screening. 

Liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) is now considered as a perfect complement to HPLC-DAD (diode array detection) and gas chromatography (GC)-MS for the general unknown screening of drugs and toxic compounds. 

Key words Liquid chromatography, Forensic and clinical toxicology. Tandem mass spectrometry. General unknown screening, Linear ion trap... 

Alternatively, Weinmann et al. have used MRM as the survey mode (14), targeting 700 compounds owing to the introduction of the scheduled MRM application (15). However, this latter hybrid technique ( multi-target screening for the first step and full scan identification for the second) cannot be regarded as a general unknown screening, as it can only detect compounds included in a predefined list. 

We describe here our LC-MS/MS general unknown screening procedure, based on a nonspecific solid-phase extraction, reverse-phase HPLC, full-scan detection and full-scan identification, which has been proved to elicit the identification of drugs from many different therapeutic classes and some of their metabolites (11). 

The windows observed after opening a general unknown screening data are presented in Fig. 1. 

Picard N, Dridi D, Sauvage FL, Boughattas NA, Marquet P (2009) General unknown screening procedure for the characterization of human drug metabolites. Application to loratadine phase I metabolism. J Sep Sci 32 2209-2217... 

The forensic toxicologist is faced with the arduous task of screening a sample for the imknown. The laboratory therefore needs to be equipped with an efficient and effective process that is able to cover a broad spectrum of toxicologically relevant substances with adequate specificity. This process is commonly referred to as either general unknown screening or systematic toxicological analysis (STA). 

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