Evaluation of direct analysis in real time mass spectrometry for onsite monitoring of batch slurry reactions

Batch slurry reactions are widely used in the industrial manufacturing of chemicals, pharmaceuticals, petrochemicals and polymers. However, onsite monitoring of batch slurry reactions is still not feasible in production plants due to the challenge in analyzing heterogeneous samples without complicated sample preparation procedures. In this study, direct analysis in real time mass spectrometry (DART-MS) has been evaluated for the onsite monitoring of a model batch slurry reaction. The results suggested that automation of the sampling process of DART-MS is important to achieve quantitative results. With a sampling technique of manual sample deposition on melting point capillaries followed by automatic sample introduction across the helium beam, relative standard deviation (RSD) of the protonated molecule signals from the reaction product of the model batch slurry reaction ranged from 6 to 30%. This RSD range is improved greatly over a sampling technique of manual sample deposition followed by manual sample introduction where the RSDs are up to 110%. Furthermore, with the semi-automated sampling approach, semi-quantitative analysis of slurry samples has been achieved. Better quantification is expected with a fully automated sampling approach.     

Newborn screening of phenylketonuria using direct analysis in real time (DART) mass spectrometry

Phenylketonuria (PKU) is commonly included in the newborn screening panel of most countries, with various techniques being used for quantification of l-phenylalanine (Phe). To diagnose PKU as early as possible in newborn screening, a rapid and simple method of analysis was developed. Using direct analysis in real time (DART) ionization coupled with triple-quadrupole tandem mass spectrometry (TQ-MS/MS) and with use of a 12 DIP-it tip scanner autosampler in positive ion mode, we analyzed dried blood spot (DBS) samples from PKU newborns. The concentration of Phe was determined using multiple reaction monitoring mode with the nondeuterated internal standard N,N-dimethylphenylalanine. The results of the analysis of DBS samples from newborns indicated that the DART-TQ-MS/MS method is fast, accurate, and reproducible. The results prove that this assay as a newborn screen for PKU can be performed in 18 s per sample for the quantification of Phe in DBS samples. DART-TQ-MS/MS analysis of the Phe concentration in DBS samples allowed us to screen newborns for PKU. This innovative protocol is rapid and can be effectively applied on a routine basis to analyze a large number of samples in PKU newborn screening and PKU patient monitoring.

Identification of Glycyrrhiza species by direct analysis in real time mass spectrometry

DART (Direct Analysis in Real Time)-MS is a novel mass spectrometric ion source, and allows the analysis of most compounds at ambient pressure and ground potential by producing [M+H]+ molecular ion species. Using this method, we examined the compounds characteristic of several kinds of licorices. For the analysis of Glycyrrhiza inflata Batalin, the peak at m/z 339 originates mainly from [M+H]+ of licochalcone A (LA), a species-specific compound. This peak was hardly detected in G. glabra Linné and G. uralensis Fischer. These results indicate that G. inflata can be differentiated from the other two species by detection of LA peaks using DART-MS analysis.     

Analysis of multiple mycotoxins in cereals under ambient conditions using direct analysis in real time (DART) ionization coupled to high resolution mass spectrometry

Direct analysis in real time (DART) ionization coupled to an (ultra)high resolution mass spectrometer based on orbitrap technology (orbitrapMS) was used for rapid quantitative analysis of multiple mycotoxins isolated from wheat and maize by modified QuEChERS procedure. After initial evaluation of ionization efficiencies for major groups of mycotoxins achievable with DART technology, sample preparation procedure and instrument parameter settings were optimized to obtain sensitive and accurate determination of most intensively ionizing toxins (deoxynivalenol, nivalenol, zearalenon, actyldeoxynivalenol, deepoxy-deoxynivalenol, fusarenon-X, altenuene, alternariol, alternariolmethylether, diacetoxyscirpenol, sterigmatocystin). The lowest calibration levels (LCLs) estimated for the respective analytes ranged from 50 to 150 μg kg⁻¹. Quantitative analysis was performed either with the use of matrix-matched standards or by employing commercially available ¹³C-labeled internal standards (available for deoxynivalenol, nivalenol and zearalenon). Good recoveries (100-108%) and repeatabilities (RSD 5.4-6.9%) were obtained at spiking level 500 μg kg⁻¹ with isotope dilution technique. Based on matrix-matched calibration, recoveries and repeatabilities were in the range 84-118% and 7.9-12.0% (RSD), respectively. The trueness of data obtained for deoxynivalenol and zearalenon in wheat/maize by DART-orbitrapMS was demonstrated by analysis of certified reference materials (CRMs). Good agreement of these results with data generated by validated ultra-high pressure liquid chromatography-time-of-flight mass spectrometry method was documented.     

New coupling of planar chromatography with direct analysis in real time mass spectrometry

The coupling of planar chromatography with direct analysis in real time time-of-flight mass spectrometry (DART-TOF-MS) was shown for the first time. Cutting the plate within a track led to substance zones positioned on the plate edge which were directly introduced into the DART gas stream. Mass signals were obtained instantaneously within seconds. Detectability was shown in the very low ng-range per zone on the example of isopropylthioxanthone. The coupling was perfectly suited for identification and qualitative purposes, but it was initially critical for quantification of results. Analytical response (R2 0.8202) and repeatability were strongly dependent from proper manual positioning of the HPTLC plate into the electronic or vibronic excited-state gas stream of the ion source. This drawback was overcome by using stable isotope-labeled standards shown on the example of caffeine. This way, analytical response (R2 0.9892) and repeatability (RSD < +/- 5.4%, n=6) were improved to a high extent. Spatial resolution by an in-house-built plate holder system was shown to be better than 3 mm. The decay of the signal was observed. The efficacy of this new coupling was compared to a plunger-based extraction device for HPTLC/electrospray ionisation-MS. The latter device showed detectability down to the pg-range, e.g. the limit of quantification for isopropylthioxanthone was found to be 100 pg. Repeatability was comparable (RSD +/- 6.7%), however, without the need of internal standard correction. Analytical response was slightly better and showed a determination coefficient R2 of 0.9983. Similar data were obtained for caffeine as well. Spatial resolution was 2 mm or 4 mm depending on the plunger head used. The comparison showed that HPTLC/DART-TOF-MS is a useful coupling method regarding qualitative aspects and it has the potential to cope also with the difficulties of quantification if isotope-labeled standards were used or if a plate holder system is employed as initially shown.     

Rapid quality assessment of Radix Aconiti Preparata using direct analysis in real time mass spectrometry

This study presents a novel and rapid method to identify chemical markers for the quality control of Radix Aconiti Preparata, a world widely used traditional herbal medicine. In the method, the samples with a fast extraction procedure were analyzed using direct analysis in real time mass spectrometry (DART MS) combined with multivariate data analysis. At present, the quality assessment approach of Radix Aconiti Preparata was based on the two processing methods recorded in Chinese Pharmacopoeia for the purpose of reducing the toxicity of Radix Aconiti and ensuring its clinical therapeutic efficacy. In order to ensure the safety and effectivity in clinical use, the processing degree of Radix Aconiti should be well controlled and assessed. In the paper, hierarchical cluster analysis and principal component analysis were performed to evaluate the DART MS data of Radix Aconiti Preparata samples in different processing times. The results showed that the well processed Radix Aconiti Preparata, unqualified processed and the raw Radix Aconiti could be clustered reasonably corresponding to their constituents. The loading plot shows that the main chemical markers having the most influence on the discrimination amongst the qualified and unqualified samples were mainly some monoester diterpenoid aconitines and diester diterpenoid aconitines, i.e. benzoylmesaconine, hypaconitine, mesaconitine, neoline, benzoylhypaconine, benzoylaconine, fuziline, aconitine and 10-OH-mesaconitine. The established DART MS approach in combination with multivariate data analysis provides a very flexible and reliable method for quality assessment of toxic herbal medicine.     

Direct monitoring of protein-chemical reactions utilising nanoelectrospray mass spectrometry

The feasibility of nanoelectrospray mass spectrometry (nanoESI) for the direct analysis of protein chemical reactions and structural changes of proteins has been evaluated. Taking advantage of the long spraying time and the capability of nanoESI for employing a wide range of solvent conditions such as buffers and detergents, applications of monitoring reaction pathways, and dynamics have been carried out with several peptides and proteins. The time course of proteolytic digestions with trypsin and pepsin was investigated for several model polypeptides, and nanoESI showed to provide an efficient tool for optimising digestion conditions for the mass spectrometric peptide mapping analysis. Examples of specific protein chemical modification reactions at arginine and tyrosine residues illustrate the feasibility of nanoESI to monitoring reaction yields and modification sites for more than 180 min. Furthermore, changes of the pattern of protonated molecules caused by temperature effects and by protein unfolding due to disulfide bond reduction have been studied with the model proteins cytochrome c and hen eggwhite lysozyme. The results indicate that nanoESI is an efficient technique for the direct, molecular characterisation of protein-chemical reactions in solution.     

采用实时直接分析质谱法原位快速鉴别茶叶

采用近年来发展迅速的常温常压离子化技术——实时直接分析质谱法,建立了对茶叶中主要成分如茶氨酸、咖啡碱等的快速测定方法,通过特征的质谱信号离子,实现了对不同茶叶的快速鉴别。实时直接分析质谱法在大气压下进行,无需对茶叶进行任何的样品处理,大大缩短了分析时间,实现了原位、快速、准确且高通量的检测。     

Detection of illicit drugs on surfaces using direct analysis in real time (DART) time-of-flight mass spectrometry

Methamphetamine (meth) from meth syntheses or habitual meth smoking deposited on household surfaces poses human health hazards. The U.S. State Departments of Health require decontamination of sites where meth was synthesized (meth labs) before they are sold. National Institute for Occupational Safety and Health (NIOSH) methods for meth analysis require wipe sampling, extraction, clean‐up, solvent exchange, derivatization, and/or mass spectral analysis using selected ion monitoring. Rapid and inexpensive analyses could screen for drug‐contamination within structures with greater spatial resolution, provide real‐time analyses during decontamination, and provide thorough documentation of successful clean ups. Herein an autosampler/open‐air ion source time‐of‐flight mass spectrometric technique is described that required only direct sampling using cotton‐swab wipes. Each wipe sample collection required 2 min and data acquisition required only 13 s per sample. Optimum collision‐induced dissociation voltages, desorption gas temperatures, and wipe sample solvents were determined for 11 drugs. Peaks were observed in analyte‐ion traces for 0.025 µg/100 cm² of meth and seven other drugs. This level is half the detection limit of NIOSH methods and one‐fourth of the lowest U.S. state decontamination limit for meth. Dynamic ranges of 100 in concentration were demonstrated for eight drugs, which is sufficient for a screening technique. The volatilities of 11 drugs deposited on glass were determined. The pick up of the drugs by solvent‐soaked cotton‐swab wipes from glass relative to acrylic latex paint was also compared. Published in 2011 by John Wiley & Sons, Ltd.