MSACL 2026 Abstract

Is Selectivity in the “Eye” of the Beholder? The Curious Case of Vitamin A Testing

Russell P Grant (1), Meghan Norris Bradley (1), Telicia Coble (1), Imir Metushi (2), Matthew L Crawford (1)
(1) Labcorp, Burlington, NC, (2) David Geffen School of Medicine at UCLA, Los Angeles, CA

Russell Grant, PhD (Presenter) Labcorp

Presenter Bio: Dr. Grant earned a first-class honors degree in Industrial Chemistry from Cardiff University and a PhD in Chromatographic and Mass Spectrometric technologies from the University of Swansea, Wales, United Kingdom. He continued his scientific training in various industrial settings, which have included senior scientist at GSK, Principal scientist at Cohesive Technologies, Technical director at Eli Lilly, and Director of Mass Spectrometry at Esoterix Endocrinology. Dr Grant is currently the Vice President of Research and Development and co-discipline director for Mass spectrometry at Labcorp. Dr Grant has pioneered the use of direct injection technologies, chromatographic systems multiplexing, microsampling, utility of automation, and other new analytical platforms in direct patient care. His research goals are focused upon improvements in speed, sensitivity, and quality of liquid chromatography with tandem mass spectrometric (LC-MS/MS) analytical systems and assays. Dr Grant has been awarded 100 patents and received both the MSACL Distinguished contribution award and ASMS AL Yergey “Unsung Hero” Award in 2024 for his contributions to Clinical Diagnostics using Mass Spectrometry.

Relevant Financial Disclosures (within past 24 months, reported on Apr 23, 2026) Committee/Board/Advisory Board BCal Diagnostics Stock/Bonds Labcorp Salary Labcorp Conflict mitigation NOT REQUIRED.

PROBLEM:
We received an email with a question regarding a patient result due to differences between the Labcorp LC-MS/MS test result (less than the normal range) versus a second result of using LC-UV at an alternate laboratory (low but within the normal range). On the surface, one could have easily brushed this off as "mass spectrometry" is more selective but, the email also came with a comment that the physician was treating the patient with "gildeuretinol". On close examination, this compound is in fact a tri-deuterated form of vitamin A and is currently in clinical development. This troubleshooting presentation will follow the process of determining the potential for interference to fundamentally address the question, is mass spectrometry selective?

METHOD:
Pipet 100uL Serum extracted with 400ul of IPA, mix, centrifuge, inject 20uL. ARIA LX4 - API5500. MP-A: 1:1 ACN: Water, MP-B: ACN. 3 min gradient LC program, 1-2 mL/min flow rate. Column: 50x2 Luna PFP, 5µm. Quantifier and qualifier SRM acquisition for Vitamin A and D4-Vitamin A IS.

TROUBLESHOOTING STEPS:
All experiments had to be performed without gildeuretinol as Labcorp has not been able to acquire the compound to date. Troubleshooting studies were required to determine the propensity of gildeuretinol to interfere with the D4-Vitamin A IS used in the LC-MS/MS assay. Troubleshooting included the following considerations: Chromatographic peak shape review: No other peaks observed, peak shape consistent. IS response assessment: Inconclusive due to variance in IS response. Ion ratio agreement for IS: Discernable positive bias in ion ratio plot for IS indicating co-eluting contribution to qualifier transition. Ion ratio consistent for Vitamin A.

Subsequent analysis of a second patient analyzed with and without IS addition elucidated the following phenomenon. Identical chromatographic peak shapes for Vitamin A and D4-Vitamin A IS relative to the first patient (and cals/QC's). Response of IS quantifier transition ~30% higher than the batch average with IS added. When analyzing without IS, co-eluting peaks for both the quantifying and qualifying transitions for the D4-Vitamin A IS with ion ratio’s consistent with the first patient were observed (~20% more qualifying ion response versus quantifier response contribution).

OUTCOME:
The final observations (accurate mass product ion analysis, sentinel transition addition to the assay and isotope walking for the D4-Vitamin A IS) will be presented. As a cliff hanger, we pose this question, was LC-MS/MS or LC-UV the better result?