Coupling of planar chromatography with Direct Analysis in Real Time mass spectrometry

Direct Analysis in Real Time mass spectrometry (DART-MS) is an emerging and rapidly developing area of ambient desorption ionization mass spectrometric techniques. Its coupling with planar chromatography is especially promising, as compared to other ambient desorption ionization techniques, because it does not require the use of liquids that may distort the shape of a spot by diffusion effects. In the first publications on TLC/HPTLC-DART-MS, due to the fixed, horizontally aligned supply of the gas flow from the DART ionization source to the MS inlet, the introduction of HPTLC/TLC plates as cut strips was inconvenient for quantitation, and the repeatability was very low due to the manual positioning. Recently a new version of the DART ion source was suggested, which allows adjusting the angle of the DART gas stream and the use of a motorized rail, thereby, improving highly the capabilities of TLC/HPTLC-DART-MS. This comprehensive review describes the development and analytical capabilities of TLC/HPTLC-DART-MS, and the general DART-MS perspectives for surface analysis or imaging MS.      

Some new features of Direct Analysis in Real Time mass spectrometry utilizing the desorption at an angle option

The present study is a first step towards the unexplored capabilities of Direct Analysis in Real Time (DART) mass spectrometry (MS) arising from the possibility of the desorption at an angle: scanning analysis of surfaces, including the coupling of thin‐layer chromatography (TLC) with DART‐MS, and a more sensitive analysis due to the preliminary concentration of analytes dissolved in large volumes of liquids on glass surfaces. In order to select the most favorable conditions for DART‐MS analysis, proper positioning of samples is important. Therefore, a simple and cheap technique for the visualization of the impact region of the DART gas stream onto a substrate was developed. A filter paper or TLC plate, previously loaded with the analyte, was immersed in a derivatization solution. On this substrate, owing to the impact of the hot DART gas, reaction of the analyte to a colored product occurred. An improved capability of detection of DART‐MS for the analysis of liquids was demonstrated by applying large volumes of model solutions of coumaphos into small glass vessels and drying these solutions prior to DART‐MS analysis under ambient conditions. This allowed the introduction of, by up to more than two orders of magnitude, increased quantities of analyte compared with the conventional DART‐MS analysis of liquids. Through this improved detectability, the capabilities of DART‐MS in trace analysis could be strengthened. Copyright © 2011 John Wiley & Sons, Ltd.     

Evaluation of alternative sorbents for dispersive solid‐phase extraction clean‐up in the QuEChERS method for the determination of pesticide residues in rice by liquid chromatography with tandem mass spectrometry

Many compounds are used for pest control during the production and storage of rice, making it necessary to employ multiclass methods for pesticide residues determination. For this purpose, QuEChERS‐based methods are very efficient, fast and accurate, and improvements in the clean‐up step are important, especially for complex matrices, like cereals. In this work, different sorbents such as chitosan, florisil^®, alumina, diatomaceous earth, graphitized carbon black, besides the commonly used primary secondary amine and octadecylsilane, were evaluated for dispersive solid‐phase extraction clean‐up in acetate‐buffered QuEChERS method for the determination of residues of 20 representative pesticides and one metabolite in rice by liquid chromatography coupled to tandem mass spectrometry. The sorbent C18 presented the best results, however, chitosan showed similar results, and the best performance among the unconventional sorbents evaluated. The method limit of quantification, attending accuracy (70–120% recovery) and precision (RSD ≤20%) criteria, ranged from 5 to 20 μg/kg. Results showed that chitosan is an effective alternative to reduce analysis costs, maintaining the method reliability and accuracy.     

An alternative sampling algorithm for use in liquid chromatography/tandem mass spectrometry experiments

In liquid chromatography/tandem mass spectrometry (LC/MS/MS) analyses of complex peptide mixtures, dynamic exclusion functions are used to minimize repeat selections of identical precursors for collision induced dissociation (CID). We describe a new algorithm for the dynamic exclusion of m/z values during LC/MS/MS. Full-scan based peak exclusion (Fulspec) uses a simplified model of chromatographic peak formation to detect and exclude contaminants present throughout the run or that lead to broad peaks. Therefore, instead of excluding peptides from fragment analysis according to a rigidly predefined time window, the chromatographic properties of the detected analytes are used. The algorithm was tested on two datasets derived from previously published experiments. Fulspec achieves a distribution of CID spectra with minimal tailing on the retention time axis, without resorting to rigid exclusion of m/z values. The procedure further excludes intensities with a bias towards low-quality CID spectra. This combination frees up valuable analytical capacity. The underlying intensity vs. quality analyses challenge the assumption that abundant precursors automatically give the best identifications. Further validation of the algorithm will require its incorporation by equipment manufacturers into the instrument control programs.     

简便的无栅极实时直接分析质谱进样装置

设计并构建了一种简单方便的无栅极实时直接分析( DART)质谱进样装置,它由惰性载气、离子发生器、加热管以及温控部分等组成,该装置不含栅极,减少了结构单元,可与多种质谱仪联用。具有结构简单、易于构建、灵活、成本低的特点。使用构建的装置,考察了载气类型、载气流速以及加热带温度等实验条件的影响。选取氩气作载气,流速7.5 L/min,加热带温度为300℃,通过对苯乙醇和亚油酸溶液、敌敌畏乳剂、蚊香块和柑橘皮、以及薄层板上的盐酸普萘洛尔6种样品的分析结果,显示了该装置的实用性。     

Laser desorption ionization of red phosphorus clusters and their use for mass calibration in time‐of‐flight mass spectrometry

Phosphorus clusters P_n (n = 1–89) are easily formed from red phosphorus by laser desorption ionization (LDI) and they cover a range of up to approx. m/z 3000 in both positive and negative ion mode. The clusters are singly charged and the spectra are simple because phosphorus is monoisotopic. The mass spectra can be measured with an acceptable resolution and intensity. The use of positively charged P_n clusters for calibration in mass spectrometry was examined and it was demonstrated that in external calibration a standard deviation of ±0.04 m/z units can be achieved even when using a common commercial matrix‐assisted laser desorption/ionization time‐of‐flight (MALDI‐TOF) instrument. When used as internal standards the P_n clusters react with some analytes – C₆₀ and C₇₀ fullerenes and cucurbituril[8], for example. It was also found that red phosphorus is a suitable MALDI matrix for peptides and proteins, illustrated by the examples of a Calmix mixture of bradykinin, angiotensin, renin, adrenocorticotropic hormone ACTH fragment 18‐359 and insulin, and of insulin alone. Copyright © 2009 John Wiley & Sons, Ltd.     

Ion-implanted reference standards for use in microchemical analysis of materials

Summary A concise overview has been given of the present state of development of ion-implanted reference standards for the calibration of instrumental methods of microchemical characterization of solid materials.

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Ionen-implantierte Standardpräparate für die Mikroanalyse

Zusammenfassung Der gegenwärtige Entwicklungsstand ionenimplantierter Standardpräparate für die Eichung instrumenteller Mikromethoden der chemischen Feststoffanalyse wurde besprochen.

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Presented at the 8th International Microchemical Symposium, Graz, August 25–30, 1980.     

Assessment of tandem mass spectrometry and high‐resolution mass spectrometry for the analysis of bupivacaine in plasma

Triple quadrupole mass spectrometers coupled with high performance liquid chromatography are workhorses in quantitative bioanalyses. They provide substantial benefits including reproducibility, sensitivity and selectivity for trace analysis. Selected reaction monitoring allows targeted assay development but datasets generated contain very limited information. Data mining and analysis of nontargeted high‐resolution mass spectrometry profiles of biological samples offer the opportunity to perform more exhaustive assessments, including quantitative and qualitative analysis. The objectives of this study were to test method precision and accuracy, to statistically compare bupivacaine drug concentration in real study samples and to verify if high‐resolution and accurate mass data collected in scan mode can actually permit retrospective data analysis, more specifically, extract metabolite related information. The precision and accuracy data presented using both instruments provided equivalent results. Overall, the accuracy ranged from 106.2 to 113.2% and the precision observed was from 1.0 to 3.7%. Statistical comparisons using a linear regression between both methods revealed a coefficient of determination (R²) of 0.9996 and a slope of 1.02, demonstrating a very strong correlation between the two methods. Individual sample comparison showed differences from ?4.5 to 1.6%, well within the accepted analytical error. Moreover, post‐acquisition extracted ion chromatograms at m/z 233.1648 ± 5 ppm (M ? 56) and m/z 305.2224 ± 5 ppm (M + 16) revealed the presence of desbutyl‐bupivacaine and three distinct hydroxylated bupivacaine metabolites. Post‐acquisition analysis allowed us to produce semi‐quantitative evaluations of the concentration–time profiles for bupicavaine metabolites. Copyright © 2015 John Wiley & Sons, Ltd.     

N_2-DART-Orbitrap中的特征气相离子反应及在西药快速检测中的应用

采用实时直接分析(DART)离子源串联高分辨质谱Orbitrap技术(DART-Orbitrap MS),对8种市售常见西药进行有效成分分析,建立了一种快速、简便、准确测定西药中有效成分的方法.对DART离子源的离子化温度、扫描模式、操作气体种类、辅助溶剂种类及其酸碱性等实验条件进行了优化,得到最佳实验条件.实验结果表明,正谱条件下,采用N_2气作为操作气体时,待测组分准分子离子峰[M+H]+同样具有较高的灵敏度和谱图辨识度.因此,N2气可以替代昂贵的He气作为DART离子源的操作气体用于8种药物有效成分的现场实时检测.该方法具备成本低、快速和操作简便的特点.通过分析待测组分的特征碎片离子,发现了N2-DART离子源中的特征离子反应,包括氧化反应和重排反应.根据获得的特征碎片离子对N_2-DART-MS中发生的反应机理进行推导,并结合理论计算对其进行验证.N_2-DART-MS技术有望应用于复杂基质混合物的现场快速检测中.     

Quality by Design Study of the Direct Analysis in Real Time Mass Spectrometry Response

A mass spectrometry method has been developed using the Quality by Design (QbD) principle. Direct analysis in real time mass spectrometry (DART-MS) was adopted to analyze a pharmaceutical preparation. A fishbone diagram for DART-MS and the Plackett-Burman design were utilized to evaluate the impact of a number of factors on the method performance. Multivariate regression and Pareto ranking analysis indicated that the temperature, determined distance, and sampler speed were statistically significant (P < 0.05). Furthermore, the Box-Behnken design combined with response surface analysis was then employed to study the relationships between these three factors and the quality of the DART-MS analysis. The analytical design space of DART-MS was thus constructed and its robustness was validated. In this presented approach, method performance was mathematically described as a composite desirability function of the critical quality attributes (CQAs). Two terms of method validation, including analytical repeatability and method robustness, were carried out at an operating work point. Finally, the validated method was successfully applied to the pharmaceutical quality assurance in different manufacturing batches. These results revealed that the QbD concept was practical in DART-MS method development. Meanwhile, the determined quality was controlled by the analytical design space. This presented strategy provided a tutorial to the development of a robust QbD-compliant mass spectrometry method for industrial quality control.

Real time monitoring of accelerated chemical reactions by ultrasonication‐assisted spray ionization mass spectrometry

Ultrasonication has been used to accelerate chemical reactions. It would be ideal if ultrasonication‐assisted chemical reactions could be monitored by suitable detection tools such as mass spectrometry in real time. It would be helpful to clarify reaction intermediates/products and to have a better understanding of reaction mechanism. In this work, we developed a system for ultrasonication‐assisted spray ionization mass spectrometry (UASI–MS) with an ~1.7 MHz ultrasonic transducer to monitor chemical reactions in real time. We demonstrated that simply depositing a sample solution on the MHz‐based ultrasonic transducer, which was placed in front of the orifice of a mass spectrometer, the analyte signals can be readily detected by the mass spectrometer. Singly and multiply charged ions from small and large molecules, respectively, can be observed in the UASI mass spectra. Furthermore, the ultrasonic transducer used in the UASI setup accelerates the chemical reactions while being monitored via UASI–MS. The feasibility of using this approach for real‐time acceleration/monitoring of chemical reactions was demonstrated. The reactions of Girard T reagent and hydroxylamine with steroids were used as the model reactions. Upon the deposition of reactant solutions on the ultrasonic transducer, the intermediate/product ions are readily generated and instantaneously monitored using MS within 1 s. Additionally, we also showed the possibility of using this reactive UASI–MS approach to assist the confirmation of trace steroids from complex urine samples by monitoring the generation of the product ions. Copyright © 2014 John Wiley & Sons, Ltd.