Comparison of product ion spectra obtained by liquid chromatography/triple‐quadrupole mass spectrometry for library search

Abstract

Reproducibility of product ion spectra acquired using a liquid chromatography/triple-quadrupole mass spectrometry (LC/MS/MS) instrument over a 4-year period, and with three other LC/MS/MS instruments, one from the same manufacturer and two from a different manufacturer, was examined. The MS/MS spectra of 30 drug substances were generated in positive electrospray ionization mode at low, medium, and high collision energies (20, 35, and 50 eV). Purity and Fit score percentages against a 400-compound LC/MS/MS spectral library were calculated using an algorithm in which fragment intensity ratios and weighting factors were included. The long-term reproducibility study was conducted using a brand A instrument; after 4 years the reproducibility of the product ion spectra was still 94%, expressed as average Purity score. The inter-laboratory study involved two parts. Firstly, two LC/MS/MS spectral libraries, created independently in separate laboratories using brand A instruments, were compared with each other. The average Fit and Purity scores of spectra from one library against the other were better than 93 and 91%, respectively, when the same collision energies were used. Secondly, for the comparison of product ion spectra between brand A and brand B instruments, fragmentation conditions were first standardized for amitriptyline as the standard analyte. The average Fit scores of brand B spectra against the brand A spectral library varied between 79 and 85% at all three collision energies. These results indicate that, after standardizing the instrumental conditions, LC/MS/MS spectral libraries of drug substances are suitable for inter-laboratory use.

Electrospray-ionization MS/MS library of drugs as database for method development and drug identification

“…Reproducibility from lab to lab and instrument to instrument is still an unsolved problem, which is currently investigated [17][18][19][20]. Furthermore, search algorithms can still be optimised by mass spectrometry software manufacturers.…”

Recent studies on the electrospray ionisation mass spectrometric behaviour of selected nitrogen-containing drug molecules and its application to drug analysis using liquid chromatography–electrospray ionisation mass spectrometry

“…Following on from Rivier's publication, Gergov et al [10] have recently studied the reproducibility of product ion spectra acquired using a liquid chromatography triple-quadrupole tandem mass spectrometry instrument over a 4-year period and also using three other LC-MS/MS instruments, one from the same manufacturer and two from a different manufacturer. The MS/MS spectra of 30 drug substances were generated in positive ESI mode at low, medium, and high collision energies (20, 35 and 50 eV).…”

The yeast metabolome addressed by electrospray ionization mass spectrometry: Initiation of a mass spectral library and its applications for metabolic footprinting by direct infusion mass spectrometry

“…Ion source CID is in some cases instrument dependent and resulting mass spectra will also be solvent matrix dependent although standardization can partly reduce this (Bristow et al 2002). In tandem MS, the ion is pre-selected and fragmented and therefore tandem mass spectra are more specific, and the reproducibility is in general better compared to ion source region fragmentation (Bristow et al 2004;Gergov et al 2004;Josephs and Sanders 2004). In addition the sensitivity can be increase by tandem MS since the signal-tonoise ratio (S/N) can be improved dependent on the mass spectrometry technology.…”