Molecular formula analysis of fragment ions by isotope‐selective collision‐induced dissociation tandem mass spectrometry of pharmacologically active compounds

Abstract

The purpose of this work is to explore the mass fragment characterization of commonly used drugs through a novel approach, which involves isotope-selective tandem mass spectrometry (MS/MS). Collision-induced dissociation (CID) was performed with a low-resolution linear ion trap mass spectrometer in positive electrospray ionization. Three pharmacologically active ingredients, i.e. omeprazole, meloxicam and brinzolamide, selected as model compounds in their own formulation, were investigated as a sodiated adduct [C17 H19 N3 O3 S + Na](+) (omeprazole) and as protonated adducts, [C14 H13 N3 O4 S2 + H](+) and [C12 H21 N3 O5 S3 + H](+) , meloxicam and brinzolamide, respectively. Selecting a narrow window of ±0.5 m/z units, precursor ion fragmentation by CID-MS/MS of isotopologues A + 0, A + 1 and A + 2 was found very useful to confirm the chemical formula of product ions, thus aiding the establishment of characteristic fragmentation pathways of all three examined compounds. The correctness of putative molecular formula of product ions was easily demonstrated by exploiting the isotope peak abundance ratios (i.e. IF+0 /IF+1 and IF+0 /IF+2 ) as simple constraints in low-resolution MS instrumentations.

Recent (2000–2015) developments in the analysis of minor unknown natural products based on characteristic fragment information using LC–MS

“…This can be applied for the unequivocal determination of elemental composition of unknown compounds. Incidentally, the molecular formulae of product ions were reported to be determined by CID‐MS/MS fragmentation of individual isotopologs, especially when the elements having a particular isotope distribution themselves (e.g., S, Cl, Br, and Se) are present in the molecular structure (Cataldi et al, ,; Bianco et al, ).…”

Intraluminal deposits: A rare cause of glaucoma drainage implant total obstruction

“…Figure 2(c) shows the MS spectra of protonated brinzolamide [M + H] + peak at m/z 384 in the Molteno intraluminal extract. The MS/MS of the molecular ion 384 shows the presence of the precursor ion at m/z 384 along with known fragment ions 8 (Figure 2(d)), and the fragmentation pattern matched with that of 1 µg/ml brinzolamide standard solution (Figure not shown).…”

LC–PDA–MS/MS-Based Dereplication Guided Isolation of a New Optical Isomer of 19,20-Epoxycytochalasin-N and Its Cytotoxic Activity

“… 11 − 16 HRMS allows for the prediction of the molecular formula, based on the isotopic distribution pattern of the parent ions and their daughter ions. 17 , 18 This method also suggests a possible daughter ion chemical formula, which helps with the diagnosis of fragmentation loss in parent to daughter ions.…”

“…The Dictionary of Natural Products (DNP) is a comprehensive collection of the physical characteristics of 250,000 naturally occurring chemicals. To detect metabolites in extracts and biological samples, mass-based databases such as the WEIZMASS spectrum library (HRMS-based data of 3500 substances) and Metlin database are also helpful tools. − HRMS allows for the prediction of the molecular formula, based on the isotopic distribution pattern of the parent ions and their daughter ions. , This method also suggests a possible daughter ion chemical formula, which helps with the diagnosis of fragmentation loss in parent to daughter ions.…”