Normal phase chiral LC (NPLC) has been proved to be powerful and efficient for chiral separation. However, the combination of NPLC with ESI or atmospheric pressure chemical ionization MS is restricted by the poor ionization efficiency and thermal fragmentations of analytes to some extent. Direct analysis in real time MS (DART-MS) is an ambient ionization technique that shows high ionization efficiency of the analytes in the normal phase mobile phase. In this work, we coupled chiral NPLC to DART-MS for the chiral qualitative and quantitative analysis of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol and jasmonic acid enantiomers. Satisfactory results for the enantiomers of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol operating in the positive mode were obtained in terms of linearity (2.5250 mu g/mL, R-2, 0.999-1.000) and repeatability (25 mu g/mL, RSDs, 4.7-5.6%). Moreover, chiral NPLC-DART-MS resulted in the simultaneous chiral separation and detection of jasmonic acid enantiomers, which are very difficult to be analyzed by NPLC-ESI-MS and NPLC-APCI-MS. Compared with the coupled techniques of NPLC-ESI-MS and NPLC-APCI-MS, NPLC-DART-MS showed advantages in increasing the ionization efficiency and reducing the in-source thermal fragmentation of analytes.

This review article will give an up-to-date and exhaustive overview on the efficient use of electron ionization (EI) to couple liquid chromatography and mass spectrometry (LC-MS) with an innovative interface called Direct-EI. EI is based on the gas-phase ionization of the analytes, and it is suitable for many applications in a wide range of LC-amenable compounds. In addition, thanks to its operating principles, it prevents unwelcome matrix effects (ME). In fact, although atmospheric pressure ionization (API) methodologies have boosted the use of LC-MS, the related analytical methods are sometime affected by inaccurate quantitative results, due to unavoidable and unpredictable ME. In addition, API's soft ionization spectra always demand for costly and complex tandem mass spectrometry (MS/MS) instruments, which are essential to acquire an "information-rich" spectrum and to obtain accurate quantitative information. In EI a one-stage analyzer is sufficient for a qualitative investigation and MS/MS detection is only used to improve sensitivity and to cut chemical noise. The technology illustrated here provides a robust and straightforward access to classical, well-characterized EI data for a variety of LC applications, and readily interpretable spectra for a wide range of areas of research. The Direct-EI interface can represent the basis for a forthcoming universal LC-MS detector for small molecules. (C) 2011 Wiley Periodicals, Inc., Mass Spec Rev 30:1242-1255, 2011

One of the crucial tasks of pharmaceutical industry is to quantify the potential genotoxic impurities (PGIs) coming from the process of drug production. The European Medicines Agency (EMEA) imposes analytical testing limits in the order of mu g/g, depending on drug dosage and exposure period, that means the need of a sensitive and selective method of analysis. Liquid chromatography coupled to electrospray ionization mass spectrometry (LC-ESI-MS) has been demonstrated as the most versatile approach to detect PGIs in complex matrices. However, time consuming derivatization processes are needed to enhance sensitivity and selectivity, and to overcome matrix effects (ME) that may arise from active pharmaceutical ingredients (APIs) or excipients. We propose the use of the Direct-EI LC-MS as an alternative approach to detect and quantify PGIs in drug formulations. The Direct-EI LC-MS interface is based on electron ionization (El) which is well suited for the detection of low molecular weight compounds of different polarity, without derivatization and with no sign of ME. The method has been successfully applied to the detection of PGIs belonging to the class of alkylation agents. Calibration experiments show satisfactory linearity and precision data. Recoveries in low enriched samples spanned from 55 to 82%, and were not affected by ME. The method limits of detection (LODs), varying from 0.13 to 1.5 mu g/g, were satisfactory for the quantitation of the target PGIs at the level required by regulatory agencies. (C) 2011 Elsevier B.V.

An LC-MS method for the analysis of personal care and household products without sample preparation is presented. The method takes advantage of the Direct-electron ionization (EI) LC-MS interface for the quantitation of principal components, as well as for the identification of unknown or undeclared ingredients. The technique has proven its inertness toward matrix effects and the electron ionization allows quantitation and library identification. Commercially available products (shower gel, perfume, and hand cream) were diluted with methanol and injected directly into a nano-LC column. Limonene, linalool, and citral were selected as target compounds because of their use as fragrances in toiletry and detergent products. These and all other fragrances are commonly determined with GC-MS analysis, prior to sample cleanup, a procedure that can lead to analytes loss. The selected compounds are not detected with ESI because of their poor or very low response. Figures of merit and validation studies were executed and special attention was devoted to matrix-effects evaluation, because a sample preparation procedure is not involved. No matrix effects were observed, and the repeatability was excellent even after several weeks of operation. Products composition was investigated in full scan mode to determine the presence of unknown or not listed ingredients.

Identification and quantification of the metabolites of drugs and drug candidates are routinely performed using liquid chromatography-mass spectrometry (LC-MS). The best practice is to generate a standard curve with the metabolite versus the internal standard. However, to avoid the difficulties in metabolite synthesis, standard curves are sometimes prepared using the substrate, assuming that the signal for substrate and the metabolite will be equivalent. We have tested the errors associated with this assumption using a series of very similar compounds that undergo common metabolic reactions using both conventional flow electrospray ionization LC-MS and low-flow captive spray ionization (CSI) LC-MS. The differences in standard curves for four different types of transformations (O-demethylation, N-demethylation, aromatic hydroxylation, and benzylic hydroxylation) are presented. The results demonstrate that the signals of the substrates compared with those of the metabolites are statistically different in 18 of the 20 substrate-metabolite combinations for both methods. The ratio of the slopes of the standard curves varied up to 4-fold but was slightly less for the CSI method.

Better sensitivity and interface of ambient sampling/ionization mass spectrometry remain a challenge. Herein, a novel, plasma-based, ambient sampling/ionization/transmission (PASIT) integrated source in a pin-to-funnel configuration was developed for the sensitive analysis of complex samples. With the funnel sleeve directly affected by direct-current discharge plasma, PASIT combines the ability to sample/ionize analyte molecules and then efficiently collect/transport charged mass species under atmospheric pressure and consequently shows an improved sensitivity. The integrated source enhances the signal intensity by more than 2 orders of magnitude compared with the previous pin-to-plate plasma source without significant background addition. A surface limit of detection (LOD) of 130 fmol mm (2) (S/N = 3) has been achieved for clenbuterol on filter paper with an argon carrier gas. Demonstrated applications include the direct determination of active ingredients from drugs and symbolic compounds from natural plants and cholesterol from mouse brain tissue sections.