Real-time feedback about dissected tissue during the neurosurgical procedure is strongly requested. A novel direct ionization mass spectrometric method for identifying pathological differences in tissues is proposed. The method is based on simultaneous extraction of tissue lipids and electrospray ionization which allows mass spectrometric data to be obtained directly from soft tissues. The advantage of this method is the stable flow of solvent, which leads to stable time-dependent spectra. The tissues included necrotized tissues and tumor tissues in different combinations. Capability for direct analysis of samples of dissected tissues during the neurosurgical procedure is demonstrated. Data validation is conducted by compound identification using precise masses from the MS profile, MS/MS, and isotopic distribution structure analysis. The method can be upgraded and applied for real-time identification of tissues during surgery. This paper describes the technique and its application perspective. For these purposes, other methods were compared with the investigated one and the results were shown to be reproducible. Differences in lipid profiles were observed even in tissues from one patient where distinctions between different samples could be poor. The paper presents a proof of concept for the method to be applied in neurosurgery particularly and in tissue analysis generically. The paper also contains preliminary results proving the possibility of observing differences in mass spectra of different tumors.

Recently, mass-spectrometry methods show its utility in tumor boundary location.The effect of differences between research and clinical protocols such as low-and high-resolution measurements and sample storage have to be understood and taken into account to transfer methods from bench to bedside. In this study, we demonstrate a simple way to compare mass spectra obtained by different experimental protocols, assess its quality, and check for the presence of outliers and batch effect in the dataset. We compare the mass spectra of both fresh and frozen-thawed astrocytic brain tumor samples obtained with the inline cartridge extraction prior to electrospray ionization. Our results reveal the importance of both positive and negative ion mode mass spectrometry for getting reliable information about sample diversity. We show that positive mode highlights the difference between protocols of mass spectra measurement, such as fresh and frozen-thawed samples, whereas negative mode better characterizes the histological difference between samples. We also show how the use of similarity spectrum matrix helps to identify the proper choice of the measurement parameters, so data collection would be kept reliable, and analysis would be correct and meaningful. K E Y W O R D Sbrain tumor, data conversion, inline cartridge extraction, low-and high-resolution comparison, spectra stability and reproducibility | INTRODUCTIONFast tissue profiling methods for mass spectrometers allowed developing methods of rapid analysis of biological substances. [1][2][3][4][5][6][7] There are a lot of attempts to incorporate mass spectrometry into the clinical routine for surgery assistance purposes. [8][9][10][11][12] Mass spectra of complex mixtures of biological molecules, even those whose mass is up to 1000 Da, is still rather a difficult task, because of the enormous diversity of molecules contained in biological tissues. 13,14 Despite the common practice of LC-MS/MS to be used as an instrument for accurate identification of complex mixture components, it could not be used as a routine technique for rapid analyses. 15 Therefore, rapid analyses

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Several years ago the photoinduced reaction of mixed phosphonium-iodonium ylides (1) with acetylenes (2) to give λ 5 -phosphinolines (3) and substituted furans (4) was described. This reaction is one-pot, metal-free synthesis of heterocycles 3 and 4 with the yields of 40% to 80%. The reaction proceeds only in dichloromethane (DCM) at the high ylide concentrations (>0.01 mol/L). The product analysis by 31 P NMR, electrospray ionization mass spectrometry, UVvis spectrophotometry, and the dynamic light scattering study of the self-aggregation of the ylide in DCM showed a dual role of the solvent in the photoinduced reactions of mixed phosphonium-iodonium ylide: (i) at the low ylide concentrations (<0.01 mol/L), the conjugated photoinitiation of the chain reaction in DCM results in the formation of chlorine-containing products and (ii) at the high ylide concentrations (>0.01 mol/L), the photolysis mechanism is determined by self-organization of the ylide molecules to give large stable aggregates in DCM, in which the target heterocycles are synthesized. Two important issues follow from the study. First, the annulation reaction between mixed phosphonium-iodonium ylide and acetylenes occurs only when the reactive intermediates are in close proximity to one other, and, second, DCM is not inert reagent in reactions occurring with participation of radicals and in one form or another can participate in photoinduced radical reactions of various solutes.KEYWORDS annulation with acetylenes, dichloromethane, phosphonium-iodonium ylides, radical reactions, selfassembly This article is dedicated with respect and affection to the memory of the late Prof. Nikolay S. Zefirov.

Detection of the brain tumor margins is one of the most significant problems in neurosurgery. Several mass spectrometry-based approaches have been proposed recently for tumor boundary detection. One of them, spray from tissue does not require sample preparation but needs special algorithms for analysis of its spectra. Here we proposed the feature selection algorithm designed for analysis of spray-from-tissue data.

The present work deals with deconvolution of interfered peaks of protonated and sodiated phosphatidylcholines to solve the problem of relative quantitation of these compounds. The method was developed based on the fact that adducts of phosphatidylcholines with proton and sodium ion give unique characteristic peaks in tandem mass spectrometry. Ultrahigh-resolution Fourier-transform ion cyclotron resonance mass spectrometry was used to resolve interfered peaks and thus validate the results of tandem mass spectrometry-based deconvolution. Applicability of the method was tested with synthesized phosphatidylcholines and applied for tissue-spray analysis of the clinical samples and demonstrated good correlation (0.996) between MS/MS and Fourier-transform ion cyclotron resonance mass spectrometry results.

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Ambient ionization mass spectrometry has become one of the most promising approaches for rapid and high-throughput screening of small molecules in complex biological matrices for emergency medicine, forensics, and food and agriculture applications. The simple procedures for sample collection and ionization without additional pretreatment are vital in these fields. Many efforts have been devoted to modifying various ambient ionization techniques to simplify the procedures and improve the robustness and sensitivity of the methods. Here, we demonstrate the implementation of rigid spherical sampler probes to improve the robustness of touch spray ionization mass spectrometry. The sphericity of the probes increases the stability of the cone-jet mode of electrospray, reduces the requirements for fine positioning of a sampler in the ion source, and decreases the possibility of corona discharge occurrence. The utilization of spherical sampler probes allows fast, non-invasive sampling, followed by rapid analysis for various drugs of different chemical classes in complex biological matrices, such as the whole blood or sebum collected from the skin surface. The linearity of the analytical signal response from drug concentration confirms the possibility of creating a simple semiquantitative method for small molecules monitoring using spherical sampler probes.