RATIONALE
The determination of the center-of-mass energy at which 50% of a precursor ion decomposes (Ecom50) during collision-induced dissociation (CID) is dependent on the chemical structure of the ion as well as the physical and electrical characteristics of the collision cell. The current study was designed to identify variables influencing Ecom50 values measured on four different mass spectrometers.
METHODS
Fifteen test compounds were protonated using +ve electrospray ionization and the resulting ions were fragmented across a range of collision energies by CID. Survival yield versus collision energy curves were then used to calculate Ecom50 values for each of these [M+H]+ ions on four different mass spectrometers. In addition, the relative recovery of the [M+H]+ ions of eight compounds ranging in molecular weight from 46 to 854 Da were determined at collision cell RF voltages ranging from 0 to 600 V.
RESULTS
Ecom50 values determined on the four instruments were highly correlated (r2 values ranged from 0.953 to 0.992). Although these overall correlations were high, we found different maximum ion recoveries depending on collision cell RF voltage. High mass ions had greater recovery at higher collision cell RF voltages, whereas low mass ions had greater recovery at lower collision cell RF voltages as well as a broader range of ion recoveries.
CONCLUSIONS
Ecom50 values measured on four different instruments correlated surprisingly well given the differences in electrical and physical characteristics of the collision cells. However, our results suggest caution when comparing Ecom50 values or CID spectra between instruments without correcting for the effects of RF voltage on ion transfer efficiency.
In real-world Lynch syndrome management, incomplete clinical follow-up was the major barrier to do genetic testing. Targeted screening costs 2- to 7.5-fold less than universal and rarely misses Lynch syndrome cases. Future changes in testing costs will likely change the optimal algorithm.
Introduction Drug options for VTE prophylaxis are increasing for ambulatory cancer patients and data regarding anticoagulant-drug interactions and their relationship to VTE and bleeding are needed to improve care. Methods Over one year, 108 cancer patients with high VTE risk were prospectively identified. Potential anticoagulant-drug interactions were ascertained by chart review and graded on need for intervention. Providers selected anticoagulant prophylaxis based on potential drug interactions and patient-provider discussion. A cross-sectional analysis was performed thereafter to evaluate VTE and bleeding endpoints within one year of anticoagulant initiation. Results The average number of potential drug interactions per patient was higher for warfarin than others (3.04 vs. 1.28 (apixaban), 1.02 (rivaroxaban), and 0.98 (LMWH)). The severity of the interactions based on grade was, for apixaban: 1.6% grade X, 50.8% grade D, and 47.5% grade C; for rivaroxaban: 2.1% grade X, 64.9% grade D, 33.0% grade C; for LMWH, 0% grade X, 66.7% grade D, 33.3% grade C; and for warfarin, 0% grade X, 29.4% grade D, 70.6% grade C. At the end of the investigational period, 11 bleeds and 7 VTEs were reported. Drug combinations significantly associated with an increased bleeding risk were crizotinib with apixaban or rivaroxaban and PPIs with warfarin. The use of sulfamethoxazole-trimethoprim with warfarin was associated with an increased VTE risk. Conclusions DOACs had fewer DDIs than warfarin, although interaction severity differed between anticoagulants. Some anticoagulant-drug interactions were associated with bleeding or VTE. Although not powered for analysis, DDI severity did not affect bleeding rates and inversely correlated with VTE risk.
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