Discovery and targeted monitoring of polychlorinated biphenyl metabolites in blood plasma using LC-TIMS-TOF MS

Abstract

In the present work, the potential for rapid, targeted analysis of hydroxylated metabolites of polychlorinated biphenyls (OH-PCBs) in diluted human blood plasma using liquid chromatography coupled with trapped ion mobility spectrometry and TOF high resolution mass spectrometry (LC-TIMS-TOF MS) was evaluated. Experimental OH-PCB collisional cross section (CCS) and gas-phase candidate structures (<3% error) are reported for the first time and used, in addition to the LC retention time and accurate /, as OH-PCB identification features in order to increase the detection selectivity. The proposed LC-TIMS-TOF MS workflow combines a "dilute-and-shoot" sample preparation strategy, a robust liquid chromatography step, a high-resolving power mobility separation (R ~ 150-250) and high-resolution mass spectrometry (R ~ 30-40k) for the separation, identification and quantification of common OH-PCB isomers with limits of detection comparable to traditional workflows (e.g., LOD and LOQ of ~10 pg/mL and ~50 pg/mL, respectively). The higher selectivity and low detection limits provides multiple advantages compared to current methodologies that typically require long, labor-intensive preparation and/or derivatization steps prior to gas or liquid chromatography-mass spectrometry.

Utilizing Ion Mobility-Mass Spectrometry to Investigate the Unfolding Pathway of Cu/Zn Superoxide Dismutase

“…The masses of 63 Cu and 64 Zn differ by only 0.999545 Da ( Rhoads et al, 2013 ) and have overlapping isotopic distributions. Furthermore, large proteins often exhibit a broad isotopic distribution due to the natural abundance of 13 C and other isotopes, making the assessment of metal amounts for copper and zinc exceedingly difficult ( Rhoads et al, 2011 ; Xian et al, 2012 ; Rhoads et al, 2013 ; Adams et al, 2018 ). This was previously observed in single-metal SOD1 measured from the spinal cord tissue of transgenic mice where the authors were also unable to distinguish between copper-containing, zinc-deficient SOD1 and the zinc-containing, copper-deficient form of SOD1 due to the overlap of the protein isotopic distribution ( Rhoads et al, 2011 ).…”

Pathways to Understanding Virus-Host Metabolism Interactions

“…These instruments are now commercially available. During IM, ions interact with a drift gas that enables separation based on structure [77,78]. As IM techniques, software and databases for metabolites and lipids are further developed its possible benefits to metabolomics and lipidomics will become more clear.…”

“…IM can be coupled to UHLPC and GC. Together, these approaches allow for multiple dimensions to metabolite identification and quantification: e.g., UHLPC retention time, IM "drift time", high resolution parent ion and fragment ion information [77,79]. Importantly, these techniques separate compounds based on the chemical and/or structural nature of metabolites and lipids.…”

Evidence of Cis/Trans-Isomerization at Pro7/Pro16 in the Lasso Peptide Microcin J25

“…The push for higher resolution and more sensitivity IMS-MS has led, among others, to the development of trapped IMS-MS (TIMS-MS) [28][29][30]. TIMS-MS has been effective in a variety of bioanalytical studies, including small molecules [31,32], peptides [33][34][35], proteins [36][37][38], DNA [39,40], polymers [41], petroleomics [42], lipidomics [43] and proteomics [44,45]. Remarkable is the potential of TIMS for the separation of isomers in mixtures, due to the high mobility resolving power [46][47][48].…”