Mass Measurement Of Product Ions Research Articles

Hemp Chemotype Definition by Cannabinoids Characterization Using LC-ESI(+)-LTQ-FTICR MS and Infrared Multiphoton Dissociation

The development and application of advanced analytical methods for a comprehensive analysis of Cannabis sativa L. extracts plays a pivotal role in order to have a reliable evaluation of their chemotype definition to guarantee the efficacy and safety in pharmaceutical use. This paper deals with the qualitative and quantitative determination of cannabidiol (CBD), tetrahydrocannabinol (THC), cannabinol (CBN), tetrahydrocannabivarin (THCV), cannabidivarin (CBDV), and cannabigerol (CBG) based on a liquid chromategraphy-mass spectrometry (LC-MS) method using electrospray ionization in positive mode (ESI+), coupled with a hybrid quadrupole linear ion trap (LTQ) and Fourier transform ion cyclotron resonance mass spectrometer (FTICR-MS). For the first time, structural information of phytocannabinoids is available upon precursor ions’ isolation within the FTICR trapping cell and subsequent fragmentation induced by infrared multiphoton dissociation (IRMPD). Such fragmentation and accurate mass measurement of product ions, alongside collision-induced dissociation (CID) within LTQ, was advantageous to propose a reliable fragmentation pattern for each compound. Then, the proposed LC-ESI(+)-LTQ-FTICR MS method was successfully applied to the hemp chemotype definition of three registered Italian accessions of hemp C. sativa plants (Carmagnola C.S., Carmagnola, and Eletta Campana), thus resulting in the Eletta Campana accession being the best one for cannabis product manufacturing.

Fingerprint analysis of Gelsemium elegans by HPLC followed by the targeted identification of chemical constituents using HPLC coupled with quadrupole-time-of-flight mass spectrometry

Gelsemium elegans, which is a genus of the family Loganiaease, is commonly used as a traditional medicine for promoting animal growth and treating rheumatoid arthritis pain and neuropathic pain, among others. In this study, we first established a valid high-performance liquid chromatography (HPLC) method for the fingerprint analysis of Gelsemium elegans samples. Then, the comprehensive detection of chemical constituents from the samples was performed using HPLC coupled with quadrupole-time-of-flight mass spectrometry. The similarity evaluation results showed that location and area differences influenced the quality of the samples. An efficient strategy for the rapid targeted identification of chemical components was matching with a developed Gelsemium database. As a result, the accurate elemental compositions and known structures of compounds are found as hits. This process facilitated the structural identification of compounds combined with the accurate mass measurement of product ions and fragmentation behaviors. Consequently, 41 components including six alkaloids and non-alkaloids were systematically identified from Gelsemium elegans. The results showed that at least seven relatively major components existing in Gelsemium elegans may be useful for its quality control. The present analytical method combined with the developed Gelsemium database was shown to be a useful tool for investigating the chemical components of Gelsemium products.

A Novel Salt Bridge Mechanism Highlights the Need for Nonmobile Proton Conditions to Promote Disulfide Bond Cleavage in Protonated Peptides Under Low-Energy Collisional Activation

The gas-phase fragmentation mechanisms of small models for peptides containing intermolecular disulfide links have been studied using a combination of tandem mass spectrometry experiments, isotopic labeling, structural labeling, accurate mass measurements of product ions, and theoretical calculations (at the MP2/6-311 + G(2d,p)//B3LYP/3-21G(d) level of theory). Cystine and its C-terminal derivatives were observed to fragment via a range of pathways, including loss of neutral molecules, amide bond cleavage, and S-S and C-S bond cleavages. Various mechanisms were considered to rationalize S-S and C-S bond cleavage processes, including charge directed neighboring group processes and nonmobile proton salt bridge mechanism. Three low-energy fragmentation pathways were identified from theoretical calculations on cystine N-methyl amide: (1) S-S bond cleavage dominated by a neighboring group process involving the C-terminal amide N to form either a protonated cysteine derivative or protonated sulfenyl amide product ion (44.3 kcal mol(-1)); (2) C-S bond cleavage via a salt bridge mechanism, involving abstraction of the alpha-hydrogen by the N-terminal amino group to form a protonated thiocysteine derivative (35.0 kcal mol(-1)); and (3) C-S bond cleavage via a Grob-like fragmentation process in which the nucleophilic N-terminal amino group forms a protonated dithiazolidine (57.9 kcal mol(-1)). Interestingly, C-S bond cleavage by neighboring group processes have high activation barriers (63.1 kcal mol(-1)) and are thus not expected to be accessible during low-energy CID experiments. In comparison to the energetics of simple amide bond cleavage, these S-S and C-S bond cleavage reactions are higher in energy, which helps rationalize why bond cleavage processes involving the disulfide bond are rarely observed for low-energy CID of peptides with mobile proton(s) containing intermolecular disulfide bonds. On the other hand, the absence of a mobile proton appears to "switch on" disulfide bond cleavage reactions, which can be rationalized by the salt bridge mechanism. This potentially has important ramifications in explaining the prevalence of disulfide bond cleavage in singly protonated peptides under MALDI conditions.

Characterization of carbofuran photodegradation by‐products by liquid chromatography/hybrid quadrupole time‐of‐flight mass spectrometry

The structural elucidation of by-products arising from carbofuran photodegradation using a high-pressure UV lamp has been investigated by liquid chromatography/electrospray ionization tandem mass spectrometry (LC/ESI-MS/MS) employing a quadrupole time-of-flight mass spectrometer. Exact mass measurements of the [M + H]+ ions of the by-products and of product ions allowed the elemental formulae and related structures of seven photodegradation by-products (resulting, respectively, from photo-Fries rearrangement, hydroxylation of the benzene ring, oxidation of the 2,3-dihydrobenzofuran ring, cleavage of the carbamate group, hydrolysis of the ether group and the newly observed radical coupling and decarboxylation processes) to be determined confidently. Accurate mass measurements of product ions allowed ambiguities to be removed concerning neutral losses having the same nominal mass, namely CO and C2H4, allowing the fragmentation patterns to be rationalized.

Exact mass measurement of product ions for the structural confirmation and identification of unknown compounds using a quadrupole time‐of‐flight spectrometer: a simplified approach using combined tandem mass spectrometric functions

This article describes a simple method to perform lock mass corrected accurate mass measurements in tandem mass spectrometry (MS/MS) with a quadrupole time-of-flight (Q-TOF) mass spectrometer. The experimental approach consists of using the protonated molecule of a known compound, which is measured in a MS/MS function using low collision energy (no fragmentation), as mass calibrator. The unknown compound is acquired in MS/MS mode albeit using high collision energy. After the acquisition, the two MS/MS spectra of unknown and mass calibrator are combined, and the fragments of the unknown are lock mass corrected by using the protonated molecule of the mass calibrator. To prove this concept, 10 compounds were analyzed using this approach, the fragments interpreted and, where possible, related to structural data available in the literature. All the unequivocally assigned fragments were accurately mass measured with mass errors within appropriate limits, i.e. for m/z values <200 with a mass tolerance of 3 mDa while for m/z > 200 the mass tolerance is expressed as 10 ppm.

Exact mass measurement of product ions for the structural elucidation of drug metabolites with a tandem quadrupole orthogonal-acceleration time-of-flight mass spectrometer

We herein report upon an approach whereby the interpretation of tandem mass spectrometry spectra can be both expedited and simplified via the accurate mass assignment of product ions utilizing a tandem quadrupole time-of-flight mass spectrometer (QqTOF). The applicability of the QqTOF in the drug metabolism laboratory is illustrated by the elucidation and differentiation of the dissociative pathways for Bosentan and its hydroxylated and demethylated metabolites. Target analyte fragmentation mechanisms were readily achieved by the measurement of product ions with a mass accuracy <5 ppm, possible by single-point internal recalibration using the residual precursor ion as calibrant. Differentiation of both precursor and product ions from nominally isobaric matrix species derived from biological extracts is demonstrated by operation of the QqTOF at resolutions of ∼8000 ( m/Δm FWHM).

A preliminary study using fast gradient liquid chromatography coupled to a quadrupole orthogonal time-of-flight mass spectrometer

The combination of a quadrupole orthogonal time-of-flight (Q-TOF) mass spectrometer with fast chromatography has been studied. It was found that the combination was capable of giving good accuracy of mass measurement for mass spectra with errors generally better than 5 ppm. In addition it was shown that mass measurement of product ions was also possible despite the relatively few scans available across the fast chromatographic peaks. Copyright © 1999 John Wiley & Sons, Ltd.

High resolution accurate mass measurement of product ions formed in an electrospray source on a sector instrument

AbstractThe high resolution accurate mass measurement of product ions formed by collisionally activated dissociation in an electrospray source has been achieved using a reversed‐geometry double‐focusing mass spectrometer and accelerating voltage scans. Accurate mass measurements of product ions from angiotensin I, angiotensin II, leucine enkephalinamide, substance P (1–9) and a synthetic compound of pharmaceutical interest were obtained with an average error of &lt;5 ppm.