Evaluation of a High Resolving Power Time-of-Flight Mass Spectrometer for Drug Analysis in Terms of Resolving Power and Acquisition Rate

Abstract

Liquid chromatography time-of-flight mass spectrometry (LC-TOFMS) is applied increasingly to various fields of small molecule analysis. The moderate resolving power (RP) of standard TOFMS instruments poses a risk of false negative results when complex biological matrices are to be analyzed. In this study, the performance of a high resolving power TOFMS instrument (maXis by Bruker Daltonik, Bremen, Germany) was evaluated for drug analysis. By flow injection analysis of critical drug mixtures, including a total of 17 compounds with nominal masses of 212-415 Da and with mass differences of 8.8-23.5 mDa, RP varied from 34,400 to 51,900 (FWHM). The effect of acquisition rate on RP, mass accuracy, and isotopic pattern fit was studied by applying 1, 2, 5, 10, and 20 Hz acquisition rates in a 16 min gradient elution LC separation. All three variables were independent of the acquisition rate, with an average mass accuracy and isotopic pattern fit factor (mSigma) of 0.33 ppm and 5.9, respectively. The average relative standard deviation of RP was 1.8%, showing high repeatability. The performance was tested further with authentic urine extracts containing a co-eluting compound pair with a nominal mass of 296 Da and an 11.2 mDa mass difference. The authentic sample components were readily resolved and correctly identified by the automated data analysis. The average RP, mass accuracy, and isotopic pattern fit were 36,600, 0.9 ppm, and 7.3 mSigma, respectively.

Boundaries of Mass Resolution in Native Mass Spectrometry

“…For denatured proteins up to 148 kDa baseline isotopic resolution has been reported with these instruments [9,10]. Also recent developments in TOF technology come within the realm of ultrahigh mass resolution with R ~ 50,000 being reported [11][12][13][14].…”

Non-targeted screening approaches for contaminants and adulterants in food using liquid chromatography hyphenated to high resolution mass spectrometry

“…Applying a lock mass calibration can provide smaller mass accuracies, especially for instruments that are susceptible to large mass accuracy drift [56,58,60]. If less than 3 ppm mass error is routinely achievable, this mass window can be used in a targeted search for analytes in a molecular database.…”

Multi-Target Screening of Biological Samples Using LC–MS/MS: Focus on Chromatographic Innovations

“…They are widely used in forensic toxicology due to possibility of retrospective data processing without re-analysis, which may be very useful in doping control or for the determination of emerging designer drugs [51,101]. If the resolving power, the isotopic pattern, and the mass accuracy are correctly interpreted, LC-TOF/MS presents clear benefits in terms of stability and repeatability, independently of the acquisition rate, which is of high importance when combined with UHPLC technology [101].…”

“…They are widely used in forensic toxicology due to possibility of retrospective data processing without re-analysis, which may be very useful in doping control or for the determination of emerging designer drugs [51,101]. If the resolving power, the isotopic pattern, and the mass accuracy are correctly interpreted, LC-TOF/MS presents clear benefits in terms of stability and repeatability, independently of the acquisition rate, which is of high importance when combined with UHPLC technology [101]. The combination of (UHP)LC with TOF/MS has been already successfully used in toxicology, for example for the multi-target screening of numerous drugs of abuse, over-the-counter medications, and synthetic cannabinoids in urine and plasma samples [102], doping agents in urine [103], veterinary drugs in urine [104], or drugs future science group Review Kohler & Guillarme and metabolites in postmortem blood samples [105].…”