Mass Spectrometric Techniques Research Articles

New horizons in microparticle forensics: Actinide imaging and detection of 238Pu and 242mAm in hot particles.

Micrometer-sized pollutant particles are of highest concern in environmental and life sciences, cosmochemistry, and forensics. From their composition, detailed information on origin and potential risks to human health or environment is obtained. We combine secondary ion mass spectrometry with resonant laser ionization to selectively examine elemental and isotopic composition of individual particles at submicrometer spatial resolution. Avoiding any chemical sample preparation, isobaric interferences are suppressed by five orders of magnitude. In contrast to most mass spectrometric techniques, only negligible mass is consumed, leaving the particle intact for further studies. Identification of actinide elements and their isotopes on a Chernobyl hot particle, including 242mAm at ultratrace levels, proved the performance. Beyond that, the technique is applicable to almost all elements and opens up previously unexplored scientific applications.

Comparative Assessment of Cooking Emission Contributions to Urban Organic Aerosol Using Online Molecular Tracers and Aerosol Mass Spectrometry Measurements

Cooking organic aerosol (COA) is an important source of particulate pollutants in urbanized regions. Yet, the diversity and complexity of COA components make direct identification and quantification of COA difficult. In this study, we conducted collocated OA measurements with an aerosol mass spectrometer (AMS) and a thermal desorption aerosol gas chromatography-mass spectrometer (TAG) in Shanghai. Cooking molecular tracers (e.g., C18 fatty acids, azelaic acid) measured by TAG provide unambiguous source information for evaluating the tracer ion (C6H10O+, m/z 98) used for identification and apportionment of COA in AMS analysis. Based on the collocated AMS and TAG measurements, two COA factors, namely, a primary COA (PCOA) and an oxygenated COA (OCOA) produced from rapid oxygenation of freshly emitted PCOA, were identified. Criteria for identifying COA factors from AMS analysis with different oxygenation levels are proposed, i.e., characteristic mass spectra, temporal variations, etc. Furthermore, two positive matrix factorization approaches, namely, AMS-PMF and the molecular marker (MM)-PMF, were compared for COA quantification, where high consistency was found with the contribution of COA to total PM2.5 mass estimated to be 9 ± 7% by AMS-PMF and 6 ± 5% by the MM-PMF. Our study highlights the important impacts of cooking activities on air quality in urban areas. We also demonstrate the advantage of conducting collocated measurements using multiple high time resolution mass spectrometric techniques in advancing our understanding of atmospheric OA chemistry and improving the accuracy of source apportionment.

Characterization of equine liver microsome-generated metabolites of growth hormone secretagogue small molecule ibutamoren.

Interest in growth hormone secretagogues has intensified during the past several years based on capable, ever-widening investigational applications of recombinant growth hormone in animals and humans. Ibutamoren is a potent, long-acting, selective and orally active non-peptide growth hormone secretagogue, which has a great potential for abuse as a performance-enhancing agent in sports. To support drug metabolism and pharmacokinetic studies of chiral pharmaceuticals, it is necessary to combine the resolving power of high-performance liquid chromatography with the sensitivity of mass spectrometric techniques. This paper describes the metabolic conversion of ibutamoren using equine liver microsomes and metabolite characterization using a QExactive high-resolution mass spectrometer. A total of 32 metabolites for ibutamoren (20 phase I and 12 phase II) were detected. The important findings of the current research are as follows: (1) the growth hormone secretagogue ibutamoren was prone to oxidation, resulting in corresponding hydroxylated metabolites; (2) in ibutamoren, the dissociation of the phenyl ring and 2-amino-2-methylpropanamide side chain was also observed; (3) the glucuronic acid conjugates of mono-, di- and trihydroxylated analogues were detected; and (4) no sulfonic acid conjugated metabolites were observed in this study of ibutamoren. The reported data help in the speedy detection of the growth hormone secretagogue ibutamoren and reveal its illegal use in competitive sports.

Unravelling discolouration caused by iron-flavonoid interactions: Complexation, oxidation, and formation of networks

Iron-flavonoid interactions in iron-fortified foods lead to undesirable discolouration. This study aimed to investigate iron-mediated complexation, oxidation, and resulting discolouration of flavonoids by spectrophotometric and mass spectrometric techniques. At pH 6.5, iron complexation to the 3–4 or 4–5 site instantly resulted in bathochromic shifting of the π → π* transition bands, and complexation to the 3ʹ-4ʹ site (i.e. catechol moiety) induced a π → dπ transition band. Over time, iron-mediated oxidative degradation and coupling reactions led to the formation of hydroxybenzoic acid derivatives and dehydrodimers, respectively resulting in a decrease or increase in discolouration. Additionally, we employed XRD, SEM, and TEM to reveal the formation of insoluble black metal-phenolic networks (MPNs). This integrated study on iron-mediated complexation and oxidation of flavonoids showed that the presence of the C2–C3 double bond in combination with the catechol moiety and either the 4-carbonyl or 3-hydroxyl increased the intensity of discolouration, extent of oxidation, and formation of MPNs.

Maternal and fetal metabolomic alterations in maternal lipopolysaccharide exposure-induced male offspring glucose metabolism disorders.

Maternal lipopolysaccharide (LPS) exposure during pregnancy induces metabolic abnormalities in male offspring, but the underlying mechanisms remain unclear. The purpose of this study was to investigate the effects of maternal LPS exposure during pregnancy on metabolic profiling of maternal serum and male fetal liver using Liquid Chromatograph Mass Spectrometer techniques. From day 15 to day 17 of gestation, pregnant mice were administered intraperitoneal LPS (experimental group) (50 μg/kg/d) or saline (control group). On day 18 of gestation, maternal serum and male fetal liver were collected. After LPS exposure, levels of 38 and 75 metabolites, mainly glycerophospholipid and fatty acid metabolites, were altered in maternal serum and male fetal liver, respectively. It was found that in maternal serum and male fetal livers, the glycerophospholipids containing saturated fatty acids (SFAs) and the SFAs were upregulated, while the glycerophospholipids containing polyunsaturated fatty acids (PUFAs) and the PUFAs were downregulated. This concordance between maternal and fetal alterations in glycerophospholipid and fatty acid metabolites may be a metabolomic signature of the early intrauterine period and may provide insight into the mechanisms by which maternal LPS exposure induces disorders of glucose metabolism in male offspring.

Identification of Possible Salivary Metabolic Biomarkers and Altered Metabolic Pathways in South American Patients Diagnosed with Oral Squamous Cell Carcinoma.

Oral squamous cell carcinoma (OSCC) represents 90% of oral malignant neoplasms. The search for specific biomarkers for OSCC is a very active field of research contributing to establishing early diagnostic methods and unraveling underlying pathogenic mechanisms. In this work we investigated the salivary metabolites and the metabolic pathways of OSCC aiming find possible biomarkers. Salivary metabolites samples from 27 OSCC patients and 41 control individuals were compared through a gas chromatography coupled to a mass spectrometer (GC-MS) technique. Our results allowed identification of pathways of the malate-aspartate shuttle, the beta-alanine metabolism, and the Warburg effect. The possible salivary biomarkers were identified using the area under receiver-operating curve (AUC) criterion. Twenty-four metabolites were identified with AUC > 0.8. Using the threshold of AUC = 0.9 we find malic acid, maltose, protocatechuic acid, lactose, 2-ketoadipic, and catechol metabolites expressed. We notice that this is the first report of salivary metabolome in South American oral cancer patients, to the best of our knowledge. Our findings regarding these metabolic changes are important in discovering salivary biomarkers of OSCC patients. However, additional work needs to be performed considering larger populations to validate our results.

Mass Spectrometric Biosensing: A Powerful Approach for Multiplexed Analysis of Clinical Biomolecules.

Rapid and sensitive detection of clinical biomolecules in a multiplexed fashion is of great importance for accurate diagnosis of diseases. Mass spectrometric (MS) approaches are exceptionally suitable for clinical analysis due to its high throughput, high sensitivity, and reliable qualitative and quantitative capabilities. To break through the bottleneck of MS technique for detecting high-molecular-weight substances with low ionization efficiency, the concept of mass spectrometric biosensing has been put forward by adopting mass spectrometric chips to recognize the targets and mass spectrometry to detect the signals switched by the recognition. In this review, the principle of mass spectrometric sensing, the construction of different mass tags used for biosensing, and the typical combination mode of mass spectrometric imaging (MSI) technique are summarized. Future perspectives including the design of portable matching platforms, exploitation of novel mass tags, development of effective signal amplification strategies, and standardization of MSI methodologies are proposed to promote the advancements and practical applications of mass spectrometric biosensing.

Shanpanootols G and H, Diterpenoids from the Rhizomes of Kaempferia pulchra Collected in Myanmar and Their Vpr Inhibitory Activities.

Two new trihydroxy derivative of Δ8(14),15-isopimarane diterpenoids, shanpanootols G (1) and H (2), along with three known analogues were isolated from the ethyl acetate-soluble extract of Kaempferia pulchra rhizomes collected in Shan State of Myanmar. The structures of these compounds including their absolute configurations were elucidated by the combination of one dimensional (1D) and 2D-NMR spectroscopic methods, high resolution mass spectrometric technique, and the experimental and the calculated electronic circular dichroism (ECD) data. The isopimarane diterpenoids (1-5) were tested for their Viral protein R (Vpr) inhibitory activities against TREx-HeLa-Vpr cells. Shanpanootol H (2) and (1R,2S,5S,9R,10S,13R)-1,2-dihydroxypimara-8(14),15-dien-7-one (4) exhibited anti-Vpr activities at the 5 µM treated dose.

Towards high throughput and high information coverage: advanced single-cell mass spectrometric techniques.

Mass spectrometry (MS) is attractive for single-cell analysis because of its high sensitivity, rich information, and large dynamic ranges, especially for the single-cell metabolome and proteome analysis. Efforts have been made to deal with the throughput and information coverage problems in typical manual single-cell MS techniques. In this review, advanced techniques to improve the automation and throughput for single-cell sampling and single-cell metabolome and proteome MS detection have been discussed. Furthermore, representative MS-based strategies that can increase the in-depth cellular information coverage and achieve the more comprehensive single-cell multiomics information during high throughput detection have been highlighted, providing an ongoing perspective of the MS performance for the single-cell research.

Impact of pesticide formulation excipients and employed analytical approach on relative matrix effects of pesticide determination in strawberries

Relative matrix effects between an ambient mass spectrometric technique known as coated blade spray (CBS) and liquid chromatographic separation approach when applied to multiresidue pesticide analysis in strawberry samples are explored. Acceptable slope relative standard deviations (RSD <15 %) were observed for the 9 compounds under study for both CBS-MS/MS (2.2–12.6 %) and LC-MS/MS (2.8–12.9 %) approaches. The findings signify both the elimination of relative matrix effects with the sample preparation and matrix match calibration with internal standard correction methods employed along with no matrix effect compromise made when using the direct-to-MS approach. Similarly, slopes of pesticides spiked from commercially available formulations (containing one or two pesticides) were found to not differ significantly from slopes generated with multiresidue pesticide standards (containing 24 additional pesticides besides the target 9 analytes) with either technique, highlighting the resistance of the employed methods to the excipients present in pesticide formulations in large amounts.

Mass Spectrometric Investigation of Organo-Functionalized Magnetic Nanoparticles Binding Properties toward Chalcones.

Chalcones are naturally occurring compounds exhibiting multiple biological functions related to their structure. The investigation of complexes formed by chalcones, namely 2′,4′-dihydroxy-2-methoxychalcone (DH-2-MC) and 2′,4′-dihydroxy-3-methoxychalcone (DH-3-MC), with organo-functionalized Fe3O4 magnetic nanoparticles using mass spectrometric techniques is reported. The magnetic nanoparticles were obtained by the silanization of Fe3O4 particles with 3-aminopropyltrimethosysilane, which were subsequently reacted with 3-hydroxybenzaldehyde (3-HBA) or 2-pyridinecarboxaldehyde (2-PCA), resulting in the formation of Schiff base derivatives. The formation of their complexes with chalcones was studied using electrospray (ESI) and flowing atmosphere-pressure afterglow (FAPA) mass spectrometric (MS) ionization techniques. The functional nanoparticles which were synthesized using 3-hydroxybenzaldehyde displayed higher affinity towards examined chalcones than their counterparts obtained using 2-pyridinecarboxaldehyde, which has been proved by both ESI and FAPA techniques. For the examined chalcones, two calibration curves were obtained using the ESI-MS method, which allowed for the quantitative analysis of the performed adsorption processes. The presence of Cu(II) ions in the system significantly hindered the formation of material–chalcone complexes, which was proved by the ESI and FAPA techniques. These results indicate that both mass spectrometric techniques used in our study possess a large potential for the investigation of the binding properties of various functional nanoparticles.

Application of Raman spectroscopy for the identification of phosphate minerals from REE supergene deposit

AbstractAmong critical metals, rare‐earth elements (REEs) are irreplaceable for their role in the high‐tech industry. The REE deposits commonly host REEs in fine‐grained mixtures of phosphate minerals characterized by the variable content of volatile components. However, identification of the volatile components may present challenges for laser‐ablation inductively coupled plasma mass spectrometer (LA‐ICP‐MS) and electron microprobe (EPMA) techniques. Therefore, Raman spectroscopy was applied to laterite and carbonatite samples from the Mount Weld deposit, one of the major REE deposits in Western Australia. The hydrous REE phosphate, rhabdophane, can be confidently distinguished from monazite by the presence of peaks in the region 2800–3600 cm−1. The presence of peaks at 428, 448, 579, 589, and 605 cm−1 in the Raman spectra of apatite from carbonatite allows its identification as hydroxyfluorapatite with high concentrations of F and water, and negligible Cl, SO42−, and SiO42−. The Raman spectra and composition of silcrete and carbonatite apatite are similar; thus, silcrete apatite was identified as hydroxyfluorapatite as well. The content of CO32− in both types of apatite was negligible despite the crystallization from carbonatitic magma. The aluminophosphate florencite is characterized by the presence of PO43−‐related peaks at 639, 1113, and 1609 cm−1 and H2O/OH‐related bands in the 2750–3075 cm−1 and together with rhabdophane has been identified in fine‐grained mineral mixtures. Our study demonstrates that combining Raman spectroscopy with compositional data is a powerful method for the characterization of phosphate minerals in REE deposits.

The key role of mass spectrometry in comprehensive research on new psychoactive substances

This month's Special Feature is authored by four accomplished investigators from the Department of Physical and Analytical Chemistry, University Jaume I, Castellón de la Plana, Spain. In their article, Dr. Ibáñez and colleagues direct their attention towards issues relating to new psychoactive substances (NPS), or emerging designer drugs, a heterogeneous group of compounds that aim to mimic the actions of ‘classical’ illicit drugs and circumvent scheduling guidelines. Each year these drugs contribute to a growing number of drug-related adverse events and deaths. The authors describe their work by way of a three-step strategy for the analysis of these agents by mass spectrometry: first, detection and analytical characterization of the NPS; second, metabolic and pharmacokinetics studies to select the most suitable biomarkers of their consumption; and third, the detection, identification and quantification of these biomarkers in biological tissues and fluids. They discuss the application of a range of mass spectrometric techniques, including conventional approaches such as combined liquid chromatography-mass spectrometry, but also the more recent adoption of direct ionization sources for the rapid identification of seized lots of drugs. To illustrate their points this Special Feature focuses on two model psychoactive substances: the synthetic cannabinoid XLR-11 and the synthetic cathinone 5-PPDi. Their Special Feature illustrates some of the challenges involved in the analysis of new psychoactive substances and highlights the essential role of mass spectrometry in this important and rapidly evolving area.

Electrochemical and theoretical studies on the corrosion inhibition performance of some synthesized d-Limonene based heterocyclic compounds

The present work focuses on the synthesis, structural characterization and electrochemical investigation of some heterocyclic compounds prepared from d-limonene. Firstly, 3-acetylisoxazoline was synthesized from d-limonene, this precursor is then converted to its thiosemicarbazone derivatives which were then cyclized to produce their corresponding thiazolidine-4-ones. The obtained compounds were characterized by FT-IR, 1H NMR, 13C NMR and mass spectrometric techniques. Further, DFT quantum chemical studies were also used to interpret the structural properties of the compounds using the B3LYP/6–311++G (d, p) basis set. The obtained results from experimental and theoretical studies were in good agreement showing that compounds bearing both isoxazoline and thiazolidine-4-one moieties act as good corrosion inhibitors for stainless steel in 1 M sulfuric acid.

Visualization Analysis of Glyceollin Production in Germinating Soybeans by Matrix-Assisted Laser Desorption/Ionization Mass Spectrometric Imaging Technique.

Apart from the physiological functions of soybean phytoalexins, the production sites in soybeans remain unknown. In this study, the dynamic production of phytoalexins, glyceollins, in germinating soybeans inoculated with Aspergillus oryzae was visually investigated using matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) imaging. During a 3-day sensitization using a fungus, glyceollins I-III were produced in germinating soybeans (from 0.03 mg/g for glyceollin III to 0.96 mg/g for glyceollin I). Imaging analysis provided visual evidence that glyceollins were produced only in the regions of seed coat and germinated root of the soybeans, while no production was observed in other regions, including the cotyledons. In contrast, their precursor, isoflavone, was distributed throughout the soybean. The evidence that the inoculation of the inactivated fungi also caused glyceollin production at the seed coat led us to speculate that glyceollins could be produced in the region of soybean attached to the fungus body.

Ne-22 Ion-Beam Radiation Damage to DNA: From Initial Free Radical Formation to Resulting DNA-Base Damage.

We report on the physicochemical processes and the products of DNA damage involved in Ne-22 ion-beam radiation of hydrated (12 ± 3 H2O/nucleotide) salmon testes DNA at 77 K. Free radicals trapped at 77 K were identified using electron spin resonance (ESR) spectroscopy. The measurement of DNA damage using two different techniques of mass spectrometry revealed the formation of numerous DNA products. Results obtained by ESR spectroscopy showed that as the linear energy transfer (LET) of the ion-beam radiation increases along the beam track, the production of DNA radicals correspondingly increases until just before the Bragg peak is reached. Yields of DNA products along the ion-beam track were in excellent agreement with the radical production. This work is the first to use the combination of ESR spectroscopy and mass spectrometric techniques enabling a better understanding of mechanisms of radiation damage to DNA by heavy ion beams detailing the formation of DNA free radicals and their subsequent products.

Secondary Organic Aerosol Formation from Isoprene: Selected Research, Historic Account and State of the Art

In this review, we cover selected research on secondary organic aerosol (SOA) formation from isoprene, from the beginning of research, about two decades ago, to today. The review begins with the first observations of isoprene SOA markers, i.e., 2-methyltetrols, in ambient fine aerosol and focuses on studies dealing with molecular characterization, speciation, formation mechanisms, and source apportionment. A historic account is given on how research on isoprene SOA has developed. The isoprene SOA system is rather complex, with different pathways being followed in pristine and polluted conditions. For SOA formation from isoprene, acid-catalyzed hydrolysis is necessary, and sulfuric acid enhances SOA by forming additional nonvolatile products such as organosulfates. Certain results reported in early papers have been re-interpreted in the light of recent results; for example, the formation of C5-alkene triols. Attention is given to mass spectrometric and separation techniques, which played a crucial role in molecular characterization. The unambiguous structural characterization of isoprene SOA markers has been achieved, owing to the preparation of reference compounds. Efforts have also been made to use air quality data to estimate the influence of biogenic and pollution aerosol sources. This review examines the use of an organic marker-based method and positive matrix factorization to apportion SOA from different sources, including isoprene SOA.

MO430MASS-SPECTROMETRIC IDENTIFICATION OF POST-TRANSLATIONAL GUANIDINYLATED PROTEINS IN THE CONTEXT OF SYSTEMIC LUPUS ERYTHEMATOSUS

Abstract Background and Aims With continuous identification of post-translational modified isoforms of proteins, it is becoming increasingly clear that post-translational modifications limit or modify the biological functions of native proteins are majorly involved in development of various chronic disease. This is mostly due to technically advanced molecular identification and quantification methods, mainly based on mass spectrometry. Mass spectrometry has become one of the most powerful tools for the identification of lipids. Method In this study, we used sophisticated high-resolution mass-spectrometric methods to analyze the soluble ligand of receptor Notch-3, namely the Y-box protein (YB)-1, in serum from systemic lupus erythematosus (SLE) patients. In addition, kidneys of lupus-prone (MRL.lpr) mice were analyzed by mass-spectrometric imaging techniques to identify the underlying pathomechanisms. Serum YB-1 was isolated by chromatographic methods, afterwards digested by trypsin and analyzed by matrix assisted laser desorption/ionization mass spectrometry (MALDI-MS). The kidneys were fixed in paraffin, then kidney sections were deparaffinized, tryptic digested and analyzed by mass-spectrometric imaging techniques. Mass-spectrometry of extracellular YB-1 in SLE patient serum revealed post-translational guanidinylation of two lysine’s within the highly conserved cold shock domain (CSD) of the YB-1 protein (YB-1-2G). Patients with increased disease activity and those with active renal involvement (lupus nephritis, LN) had a higher degree of dual-guanidinylation within the CSD. Of note, at least one of these modifications was present in all analyzed LN patients, whereas single-guanidinylated YB-1 was present in only one and double modification in none of the control individuals. Mass-spectrometric imaging analyses specifically localized YB-1-2G and increases Notch-3 expression in kidney sections from MRL.lpr mice. Results The data from this study clearly demonstrate the high potential of high-resolution mass spectrometric methods as well as mass spectrometric imaging techniques to identify pathomechanisms of diseases like SLE/LN.

METHOD DEVELOPMENT FOR QUANTITATIVE ANALYSIS OF NITROPROSTON IN BIOLOGICAL FLUIDS AND ITS APPLICATION IN PHARMACOKINETIC STUDY

Nitroproston is an innovation multitarget pharmaceutical based on natural prostaglandin and dinitroglycerol moety. The drug was developed for treatment of obstructive diseases in lungs including asthma and obstructive bronchitis. The goal of the presented study was to develop and validate a method for quantitative analysis of nitroproston and its main metabolites in rabbit’s plasma and its application for pharmacokinetic study of the drug. Sample preparation contained liquid-liquid extraction with ethyl acetate. For the instrumental method there was chosen high performance liquid chromatography – mass spectrometric technique that allowed to perform a quantitative analysis of the drug with high rates of accuracy and selectivity. Validation of the developed method was assessed for such parameters as: selectivity, low limit of quantification, linearity, precision and accuracy, recovery, matrix effect and stability. The method was further applied for study of pharmacokinetic parameters of nitroproston and its metabolites in rabbit’s plasma. For this purpose, six rabbits were intravenously administered with nitroproston in the dose of 25 mg/kg, where other six rabbits represented control group. Plasma samples were taken in 2, 4, 6, 4, 8, 12, 18, 24, 32 and 60 minutes after. Due to active biodegradation of nitroproston, the method was also validated for main metabolites of the drug that showed high levels of stability. As the result of the conducted validation, it was found that the method in valid for the assessed parameters. At the same time, Pharmacokinetic study of the metabolites showed that reliable profiles were received for 1,3-dinitroglycerol (first phase metabolite) and 13,14-dihydro-15keto-PGE2 (second phase metabolite).

Improved plasma stoichiometry recorded by laser ablation ionization mass spectrometry using a double-pulse femtosecond laser ablation ion source.

Femtosecond (fs) laser ablation ion sources have allowed for improved measurement capabilities and figures of merit of laser ablation based spectroscopic and mass spectrometric measurement techniques. However, in comparison to longer pulse laser systems, the ablation plume from fs lasers is observed to be colder, which favors the formation of polyatomic species. Such species can limit the analytical capabilities of a system due to isobaric interferences. In this contribution, a double-pulse femtosecond (DP-fs) laser ablation ion source is coupled to our miniature Laser Ablation Ionization Mass Spectrometry (LIMS) system and its impact on the recorded stoichiometry of the generated plasma is analyzed in detail. A DP-fs laser ablation ion source (temporal delays of +300 to - 300 ps between pulses) is connected to our miniature LIMS system. The first pulse is used for material removal from the sample surface and the second for post-ionization of the ablation plume. To characterize the performance, parametric double- and single-pulse studies (temporal delays, variation of the pulse energy, voltage applied on detector system) were conducted on three different NIST SRM alloy samples (SRM 661, 664 and 665). At optimal instrument settings for both the double-pulse laser ablation ion source and the detector voltage, relative sensitivity coefficients were observed to be closer (factor of ~2) to 1 compared with single-pulse measurements. Furthermore, the optimized settings worked for all three samples, meaning no further optimization was necessary when changing to another alloy sample material during this study. The application of a double-pulse femtosecond laser ablation ion source resulted in the recording of improved stoichiometry of the generated plasma using our LIMS measurement technique. This is of great importance for the quantitative chemical analysis of more complex solid materials, e.g., geological samples or metal alloys, especially when aiming for standard-free quantification procedures for the determination of the chemical composition.