Direct monitoring of drug degradation by easy ambient sonic-spray ionization mass spectrometry: the case of enalapril

Using enalapril maleate as a test case, the ability of ambient mass spectrometry, namely, via easy ambient sonic‐spray ionization mass spectrometry (EASI‐MS), to perform direct monitoring of drug degradation has been tested. Two manufacturing processes were investigated (direct compression and wet granulation), and the formation of degradation products was measured via both EASI‐MS and high‐performance liquid chromatography with ultraviolet detection for a total period of 18 months. Both techniques provide comparable results, which indicate that direct analysis by ambient mass spectrometric techniques presents a viable alternative for drug degradation monitoring with superior simplicity, throughput, and reliability (no sample manipulation), and comparable quantitative results. In terms of qualitative monitoring, the full mass spectra with intact species provided by EASI‐MS allow for comprehensive monitoring of known and unknown (or unexpected) degradation products. Copyright © 2011 John Wiley & Sons, Ltd.     

Study on the photostability of guaiazulene by high-performance liquid chromatography/mass spectrometry and gas chromatography/mass spectrometry

The photostability of guaiazulene (1,4-dimethyl-7-isopropylazulene; GA), a natural azulenic compound used in cosmetic and health-care products, as well as in pharmaceutical preparations, was investigated in solution (methanol, ethanol, acetonitrile), by different techniques: gas chromatography/mass spectrometry (GC/MS) and high-performance liquid chromatography combined with atmospheric pressure chemical ionization mass spectrometry and UV detection (LC/APCI-MS and HPLC/UV). A solar simulator (xenon-arc lamp) was used as UV-A radiation source. The study involved: monitoring compound decomposition, identifying products of photodegradation (PPs), assessing the role of oxygen and evaluating the kinetics of the process. Minor PPs are volatile compounds and were characterized by GC/MS, while oligomeric polyoxygenated compounds, tentatively characterized on the basis of MS and MS/MS spectra, were found to be the main photoproducts. The photodegradation was found to be enhanced by the presence of oxygen; nevertheless, determination of the singlet oxygen quantum yield for GA gave a lower value than that for the reference standard Rose Bengal. The obtained results and the developed stability-indicating methods (GC/MS and LC/MS) are of interest for stability studies and/or quality control purposes of GA as raw material or cosmetic products.     

Assessment of the degradation of polyurethane foams after artificial and natural ageing by using pyrolysis-gas chromatography/mass spectrometry and headspace-solid phase microextraction-gas chromatography/mass spectrometry

Polyurethane foams are widely present in museum collections either as part of the artefacts, or as a material for their conservation. Unfortunately many of PU foam artefacts are in poor condition and often exhibit specific conservation issues. Their fast thermal and photochemical degradations have been the aim of previous researches. It is now accepted that hydrolysis predominates for polyester-based polyurethane PU(ES) whereas oxidation is the principal cause of degradation for polyether-based polyurethane PU(ET) variety. Only a few studies have been devoted to volatile organic compounds (VOCs) emitted by polyurethanes and, to our knowledge, none were performed on polyurethane foams by using headspace-solid phase microextraction (HS-SPME). The objective of the work described here is to assess the impact of some environmental factors (humidity, temperature and daylight) on the degradation of PU foams by evaluating their volatile fractions. We investigated morphological changes, polymerized fractions and volatile fractions of (i) one modern produced PU(ES) foam and one modern PU(ET) foam artificially aged in different conditions as well as (ii) four naturally aged foams collected from various daily life objects and selected for the representativeness of their analytical data. Characterization procedure used was based on attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR), pyrolysis-gas chromatography/mass spectrometry (Py-GC/MS) and non-invasive headspace solid-phase microextraction coupled with gas chromatography and mass spectrometry (HS-SPME-GC/MS). In this paper, the formation of alcohol and acid raw products for PU(ES) and glycol derivatives for PU(ET) during natural and artificial ageing is confirmed. These main products can be considered as degradation markers for PU foams. Results show that artificial and natural ageing provide similar analytical results, and confirm that the dominant degradation paths for PU(ES) and for PU(ET) are hydrolysis and photo-oxidation, respectively. Lastly, we highlight that non-invasive HS-SPME-GC/MS analysis allows to distinguish between PU(ES) and PU(ET) at any point of their degradations.     

Benzidine photodegradation: a mass spectrometry and UV spectroscopy combined study

The benzidine photodegradation process was studied using UV/Vis spectroscopy and electrospray ionization mass spectrometry (ESI-MS) combined with collision-induced dissociation (CID) and tandem mass spectrometry (MS/MS). Mass spectrometry was used to characterize benzidine and to identify and characterize possible degradation products and intermediates. The MS data showed that benzidine is quite persistent in aqueous medium. Moreover, the MS analysis enabled us to propose the following three degradation products/intermediates: 4'-nitro-4-biphenylamine, tetrahydroxybiphenyl and 4,4'-dinitrobiphenyl. For the benzidine molecular ion and protonated molecule and for the protonated molecules of the degradation products/intermediates detected, fragmentation patterns are proposed based on CID and MS/MS data. For the photodegradation process different catalysts were used, namely the commercial TiO2 Degussa P25, and the laboratory-prepared ZnO, TiO2 anatase and a titanium-zinc oxide with a perovskite type structure. Comparison of the different catalysts showed that degradation was favoured with the commercial TiO2. Nevertheless, the other catalysts appear to be promising and economic alternatives for potential future remediation studies.     

Gas phase reactivity of isomeric arylglycosides towards amines. A chemical ionization mass spectrometry and tandem mass spectrometry study

Chemical ionization mass spectrometry (MS) and tandem mass spectrometry (MS/MS) experiments have been performed for the structural characterization and isomeric differentiation of two series of C- and O-linked arylglycosides with potential antioxidant activity. Different amines have been used for producing gas phase chemical ionization. Depending on their proton affinity and steric hindrance, adduct ions with different stability are formed. The most stable adducts are produced by ethylamine and they have been extensively structurally characterized by experimental and theoretical approaches. Energy resolved chemical ionization tandem mass spectrometric experiments have allowed unambiguous characterization and differentiation of both the anomers differing at the configuration of the glycosidic C(1) atom, and regio- and structural isomers at extremely low concentrations, typical of mass spectrometry. This study has shown that amine chemical ionization mass spectrometry and MS/MS are powerful and versatile tools for the structural characterization of arylglycosides.     

超高效液相色谱-电喷雾串联质谱法分离鉴定烟草中5种糖苷类香味前体物质

采用超高效液相色谱-电喷雾串联质谱法(UPLC-ESI MS/MS)并结合气相色谱-质谱法分离鉴定了烟草中5种主要的糖苷类香味前体物质。烟样经甲醇提取、XAD-2柱净化,得到初步纯化的糖苷,在pH 5条件下将其酶解,释放出糖苷配基。采用气相色谱-质谱分析并通过标准谱库检索确定了5种挥发性苷元;然后通过电喷雾质谱(负离子模式)确定糖苷母离子并作碎片离子扫描(MS2),确定了5种糖苷类香味前体物质的存在形式;最后采用UPLC-ESI MS/MS,以甲醇和乙酸-乙酸铵水溶液为流动相,通过RP-C18柱分离,在多反应监测(MRM)模式下,鉴定了烟草中5种主要的糖苷类香味前体物质,为应用液相色谱-质谱分析缺乏标准样品的糖苷类香味前体物质奠定了基础。     

Comprehensive chemical profiling of Guizhi Fuling capsule by the combined use of gas chromatography-mass spectrometry with a deconvolution software and rapid-resolution liquid chromatography quadrupole time-of-flight tandem mass spectrometry

Herbal formulations are complex natural mixtures. Researchers usually tend to focus more on analysis of nonvolatile components but pay less attention to volatile compounds. In this study, an analytical strategy combining two approaches was established for comprehensive analysis of herbal formulations. Guizhi Fuling capsule (GFC), a drug approved by the FDA to enter phase II clinical trial for treatment of primary dysmenorrhea, was taken as a case for analysis. Gas chromatography–mass spectrometry (GC‐MS) with automated mass spectral deconvolution and identification system (AMDIS) led to rapid identification of 48 volatile components including four acetophenones, three fatty acid esters, 13 phenylpropanoids and 19 sesquiterpenes. Most of them were found from Guizhi. The volatile oils of Guizhi have been proved to exhibit many pharmacological activities. This is helpful in understanding the pharmacological mechanism of GFC. Furthermore, AMDIS turned out to be efficient and reliable for analysis of complex herbal formulations. Rapid‐resolution liquid chromatography (RRLC) coupled with electrospray ionization quadrupole time‐of‐flight tandem mass spectrometry (ESI‐Q‐TOF MS/MS) allowed the identification of 70 nonvolatile components including six acetophenones, 12 galloyl glucoses, 31 monoterpene glycosides, three phenols and 12 triterpene acids. Fragmentation behaviors of assigned components, especially triterpene acids, which are hard to identify by low‐resolution MS, were first investigated by TOF MS/MS. Characteristic ions and typical loss of assigned triterpene acids were summarized. Combinatorial use of GC‐MS‐AMDIS and RRLC‐ESI‐Q‐TOF MS/MS could be of great help in global qualitative analysis of GFC, as well as other herbal products. Copyright © 2012 John Wiley & Sons, Ltd.     

Tandem mass spectrometry of aminated fullerene derivatives

The products of the reaction between fullerenes (C₆₀/C₇₀) and dimethylamine were investigated by fast atom bombardment (FAB) mass spectrometry and tandem mass spectrometry (MS/MS). The FAB mass spectrum shows peaks corresponding to the addition of up to eight dimethylamine species, exclusively to C₇₀. MS/MS reveals an unusual fragmentation pattern. The mass spectrum of the reaction products, together with a number of tandem mass spectra, are shown.     

Field desorption mass spectrometry of 1-methylpyridinium salts

Quaternary pyridinium salts were investigated by field desorption, field ionization and electron impact mass spectrometry. Thermal decomposition of the salts under field desorption conditions was found to give very abundant volatile products, identified as the dihydro analogues and the ‘methides’ of the cations. The formation of the volatile compounds, especially those with molecular weights corresponding to those of the (cation ?1), (cation +1) and (cation +13) was studied in detail by deuterium and ¹³C labelling experiments.     

Interactions of platinum(II) complexes with sulfur-containing peptides studied by electrospray ionization mass spectrometry and tandem mass spectrometry

Reactions of two platinum(II) complexes, cis-[Pt(NH3)2(H2O)2]2+ (Pt1) and cis-[Pt(en)(H2O)2]2+ (Pt2), with several sulfur-containing peptides, have been investigated by electrospray ionization mass spectrometry (ESI-MS) and tandem mass spectrometry (MS/MS). The species produced in the reactions were detected with ESI-MS, and MS/MS analysis was performed to probe structural information. Collision-induced dissociation revealed different dissociation pathways for the main reaction products of the two platinum(II) complexes with the same peptides. The major difference is the prominent loss of ammonia ligand for complexes of Pt1 due to the strong trans effect of sulfur, whereas the loss of ethylenediamine (en) ligand from Pt2 complexes is less favored, reflecting the chelating effect of the bidentate ligand. Despite the differences in dissociation patterns, Pt1 and Pt2, in general, form structurally similar complexes with the same peptides. In the reactions with Met-Arg-Phe-Ala they both produce a N,S-chelate ring through the N-terminal NH2 and sulfur of the Met residue, and in the reactions with Ac-Met-Ala-Ser they bind to the sulfur of Met and deprotonate an amide nitrogen upstream from the anchor site. Both of them are able to promote hydrolysis of the peptides. In reactions with glutathione they both form four-membered Pt2S2 rings and Pt-S-Pt bonding through the bridging thiolate ligand, although the reaction rate is much slower for Pt2 due to steric hindrance of the en ligand.     

Identification of the main by-products of the developing agent N-hydroxyethyl-N-ethyl-3-methyl-p-phenylenediamine in photographic effluents by liquid chromatography/mass spectrometry

N-Hydroxyethyl-N-ethyl-3-methyl-p-phenylenediamine (CD(4)) is commonly used as a developing agent in color photographic processes. The main by-products formed in developer baths used in the process were separated and identified by liquid chromatography/electron ionization mass spectrometry (LC/EI-MS) and liquid chromatography/atmospheric pressure ionization mass spectrometry (LC/API-MS). A number of side reactions, in addition to the main reactions involved in the developing process, were found to occur. Such side reactions involved in the formation of CD(4) by-products included oxidation, hydroxylation, sulfonation and the formation of coupling products. A reaction pathway for the degradation of CD(4) based on the nature of the by-products identified is proposed and discussed.     

Thermal degradation of deoxybenzoin polymers studied by pyrolysis-gas chromatography/mass spectrometry

The thermal degradation behavior of novel ultra-fire-resistant polymers and copolymers containing deoxybenzoin units in the backbone was studied by pyrolysis-gas chromatography/mass spectrometry (Py-GC/MS). The polymers were synthesized by the polycondensation of 4,4′-bishydroxydeoxybenzoin (BHDB) with isophthaloyl chloride (to give polyarylates), phenylphosphonic dichloride (to give polyphosphonates), and their mixtures (to give poly(arylate-co-phosphonate) copolymers). The thermal decomposition, under nitrogen conditions, of BHDB-polyarylate was characterized by a simultaneous degradation of both the bisphenolic (deoxybenzoin) and isophthalate sub-units, whereas a three-step decomposition phenomenon was observed for the BHDB-polyphosphonate. BHDB-polymers containing phosphonate groups in the backbone did not show any phosphorus-based volatile decomposition products, whereas the corresponding bisphenol A-based polyphosphonates released volatile decomposition products comprised mainly of phosphorus-containing compounds.     

Mapping protein interfaces by a trifunctional cross-linker combined with MALDI-TOF and ESI-FTICR mass spectrometry

Chemical cross-linking of protein complexes has gained renewed interest in combination with mass spectrometric analysis of the reaction products as it allows a rapid mapping of protein interfaces, which is crucial for understanding protein/protein interactions. The identification of cross-linking products from the complex mixtures created after the cross-linking reaction, however, remains a daunting task. To facilitate the identification of cross-linking products, we explore the use of the commercially available biotinylated cross-linking reagent sulfo-SBED (sulfosuccinimidyl-2-[6-(biotinamido)-2-(p-azidobenzamido)-hexanoamido]ethyl-1,3'-dithiopropionate). This trifunctional cross-linker possesses one amine-reactive and one photo-reactive site and, additionally, allows an affinity-based enrichment of cross-linker containing species. As a model system, we chose the Ca(2+)-dependent complex between calmodulin and its target peptide M13, which represents a part of the C-terminal sequence of the skeletal muscle myosin light chain kinase. After the cross-linking reaction, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS) and one-dimensional gel electrophoresis were employed to check for the extent of cross-linking product formation. The cross-linking reaction mixtures were subjected to tryptic in-solution digestion. Biotinylated peptides, e.g., peptides that had been modified by the cross-linker as well as cross-linked peptides, were enriched on monomeric avidin beads after several washing steps had been performed. Peptide mixtures were analyzed by MALDI-TOFMS, nano-high-performance liquid chromatography (HPLC)/nano-electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry (ESI-FTICRMS), and tandem MS. We demonstrate that an enrichment of cross-linker containing species allows a more efficient identification of interacting amino acid sequences in protein complexes. This strategy is expected to be especially beneficial for investigating large protein assemblies.     

Indigo Carmine degradation by hypochlorite in aqueous medium monitored by electrospray ionization mass spectrometry

The degradation of the dye Indigo Carmine by hypochlorite in aqueous solution was monitored by electrospray ionization mass spectrometry in the negative ion mode (ESI(—)‐MS). Hypochlorite was highly efficient in removing the color of aqueous solutions of the dye. ESI(—)‐MS monitoring showed that concomitant with the Indigo Carmine consumption two transient species appeared (detected as doubly charged anions) probably formed via a net insertion of two hydroxyl groups at the exocyclic C?C bond followed by the incorporation of two (mainly) or one oxygen atoms at the indolic rings of the dye. Structures of these products were proposed based on the ESI(—)‐MS/MS data and high accuracy mass measurements. These two transient intermediates quickly decomposed, both in the condensed and in the gas phase, to yield mono‐charged anions. Based on these results, a route for the Indigo Carmine degradation by hypochlorite in aqueous solution has been proposed. Copyright © 2007 John Wiley & Sons, Ltd.     

Characterization of photodegradation products of alachlor in water by on-line solid-phase extraction liquid chromatography combined with tandem mass spectrometry and orthogonal-acceleration time-of-flight mass spectrometry

On-line solid-phase extraction liquid chromatography in combination with mass spectrometry (MS), i.e. MS/MS and orthogonal-acceleration time-of-flight MS, was used for the characterization of photodegradation products of alachlor in river water. Various MS/MS scan functions were used, in particular the precursor-ion and the daughter-ion modes, to screen for degradation products with structures closely related to that of alachlor and to obtain information on characteristic fragments of the degradation products. Elemental compositions of compounds found and some of their fragments were calculated from the accurate mass information obtained with orthogonal-acceleration time-of-flight MS. Some ten degradation products could be characterized by combining various types of mass spectral information. Since quite a number of isomers were identified, structures of the degradation products were proposed by considering the most likely fragmentation patterns in MS/MS experiments. Degradation products of alachlor found in the current study were compared with those reported in the literature.     

Determination of binding sites in carboplatin-bound cytochrome c using electrospray ionization mass spectrometry and tandem mass spectrometry

Interaction of carboplatin with cytochrome c (Cyt. c) has been investigated by electrospray ionization mass spectrometry (ESI-MS) and tandem mass spectrometry (MS/MS). ESI-MS studies revealed that the ring-opened adducts of carboplatin with Cyt. c were formed in the stoichiometric ratio of 1:1 and 2:1 at pH 5.0 and 37 degrees C and in the stoichiometric ratio of 1:1 only at pH 7.0 and 37 degrees C. It was also found that Cyt. c could be cleaved by carboplatin at pH 2.5 and 50 degrees C. The cleaved fragments of Cyt. c were determined by ESI-MS and MS/MS analysis to be Glu66 approximately Met80, Ac-Gly01 approximately Met65, Glu66 approximately Glu104, Ac-Gly01 approximately Met80 and Ile81 approximately Glu104. The carboplatin prefers to anchor to Met65 first, then to Met80. To further confirm the binding site of Met, AcMet-Gly was used as the model molecule to investigate its interaction with carboplatin and its hydrolysis reaction. On the basis of species detected during the reaction monitored by ESI-MS, a possible pathway of the cleavage reaction was proposed.     

Characterization of linear and cyclic polylactic acids and their solvolysis products by electrospray ionization mass spectrometry

Linear and cyclic polylactic acids (PLAs) were characterized using electrospray ionization mass spectrometry (ESI-MS) as part of our ongoing investigation of the hydrolysis mechanism of biodegradable polymers. The condensation oligomers of linear polylactic acid (LPLA) were synthesized by thermal dehydration of L-lactic acid. The trimer and tetramer base polymers of cyclic polylactic acid (CPLA) were obtained by cyclization reactions of lactic acid trimers and tetramers, respectively. In the ESI-MS/MS measurement, LPLA yielded three types of product ion series, while CPLA yielded only one type, from which the repeated units of CPLA were removed. The MS/MS spectrum of the NH4+ adduct ion for both cyclic and linear PLA showed loss of one ammonia molecule. The postsource decay (PSD) spectrum of CPLA by matrix-assisted laser desorption ionization (MALDI) mass spectrometry was similar to the ESI-MS/MS spectrum, while that of LPLA was different. In addition, the degradation of cyclic and linear PLAs by solvolysis was investigated. Solvolysis with anhydrous MeOH was quite feasible, but did not readily occur in the presence of even a small amount of water in the MeOH solvent.     

Characterization of carbonyl by-products during Uniblu-A ozonation by liquid chromatography/hybrid quadrupole time-of-flight/mass spectrometry

The structural elucidation of carbonyl-containing by-products arising from Uniblu-OH ozonation has been investigated by liquid chromatography/electrospray ionization tandem mass spectrometry (LC/ESI-MS/MS) employing a quadrupole time-of-flight mass spectrometer. The by-products were derivatized with 2,4-dinitrophenylhydrazine, allowing the formation of [M-H](-) ions of the derivatives in the electrospray source. Exact mass measurements of both the [M-H](-) ions and their product ions allowed the elemental formulae and related structures of ten by-products to be determined confidently. The main degradation pathway were decarboxylation followed by further oxidation. It is noteworthy that the experimental procedure employed allowed the identification of both nitrogen- and sulphur-containing carbonyl by-products during Uniblu-OH ozonation. This result is of environmental relevance for monitoring the balance of organic nitrogen and sulphur during the ozonation of organic pollutants. These atoms, in fact, do not undergo complete mineralization.     

Sequencing of new beauverolides by high-performance liquid chromatography and mass spectrometry.

Mass spectrometry (MS) and tandem mass spectrometry (MS(n)) were used for the identification of beauverolides in the fermentation broth of Beauveria bassiana and for evaluation of the purified fraction obtained by sublimation of beauverolides. Besides being a new efficient route for purification of beauverolides, sublimation provided an enrichment of new minor lipophilic beauverolides of lower molecular weight from the original complex mycelial extract. The product ion collision-induced dissociation (CID) spectra obtained on an ion trap (electrospray ionization), the in-source CID mass spectra on a sector instrument (atmospheric-pressure chemical ionization) and the post-source decay matrix-assisted laser desorption/ionization mass spectra of beauverolides were compared and evaluated. All MS(n) experiments started with singly charged precursor ions. The following two new representatives of this group of compounds were identified by high-performance liquid chromatography and MS (HPLC/MS): cyclo-(3-hydroxy-4-methyloctanoyl-valyl-alanyl-leucyl) and cyclo-(3-hydroxy-4-methyloctanoyl-tyrosyl-alanyl-leucyl). Individual structures were confirmed by preparative isolation and nuclear magnetic resonance spectroscopy. The structure of a third novel and minor beauverolide was tentatively assigned by HPLC/MS only as cyclo-(3-hydroxy-4-methyldecanoyl-valyl-alanyl-Lxx), Lxx = leucyl, isoleucyl, or allo-isoleucyl.     

Oxidation of a laccase mediator ABTS as studied by ESI-FTICR mass spectrometry

The oxidation reaction of a laccase mediator ABTS (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) was studied by electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry (ESI-FTICRMS). Oxidation products of ABTS were measured after reaction times that varied from a few minutes up to several days and both positive and negative ionization modes were employed. Exact mass measurements and collision-induced dissociation (CID) experiments were used to characterize the structures of the ions formed. After reacting with Trametes versicolor laccase (TvL), the radical cation form of ABTS was the main product observed by the positive ionization mode. Negative ionization mode experiments revealed that a degradation product from ABTS was formed.