= Discovery stage. (16.60%, 2024)
= Translation stage. (37.02%, 2024)
= Clinically available. (46.38%, 2024)
MSACL 2024 : Bazydlo

MSACL 2024 Abstract

Self-Classified Topic Area(s): Small Molecule > Cases in Clinical Analysis > none

Podium Presentation in Steinbeck 1 on Thursday at 15:05 (Chair: Xander van Wijk / Michael Pikulski)

Untargeted Analysis Using LC-QTOF in a Pediatric Clinical Toxicology Case

Lindsay AL Bazydlo, Abigail Kerns, Christopher Holstege
University of Virginia, Charlottesville, VA

Lindsay Bazydlo, PhD (Presenter)
University of Virginia

Presenter Bio: EDUCATION:
Graduate School: University of Virginia (Chemistry), Charlottesville, VA
Clinical Chemistry and Laboratory Medicine Fellowship: University of Virginia, Charlottesville, VA

Laboratory testing in Clinical Chemistry, Toxicology, Hemostasis, and Endocrinology.

Liquid chromatography mass spectrometry assay methods.


Case Description: A 3-year-old female with no prior medical history presented to the emergency department with lethargy. She had been in her baseline state of health and visited her grandparents. Her mother arrived to find her difficult to rouse from sleep. The mother denied any possible exposure to medication. Examination was notable for a somnolent patient who awoke with stimulation but rapidly drifted back to sleep. Her blood pressure was 103/55 mmHg, pulse 88 beats per minute, respirations 24 breaths per minute, and temperature 36.5 °C. Her pupils were miotic, but the remainder of the examination was unremarkable. Basic laboratory studies were unremarkable. Urine drug immunoassay was negative. Urinalysis was positive for leukocyte esterase. Toxicology was consulted for change in mental status without clear etiology. The patient steadily improved over the next 12 hours without intervention and was discharged.

Background: Lethargy is a common, yet non-specific, reason for presentation to the pediatric emergency department. The differential diagnosis is broad and can include ingestion of an unknown substance. Current urine drug screening includes multiple different drug classes. However, tests are poorly sensitive and specific and do not exclude ingestion.

MS Method and Results: An untargeted screening approach was utilized employing LC-QTOF. The urine sample obtained from the patient was hydrolyzed with glucuronidase, diluted with solvent and injected onto the instrument. The analyzed data was processed using multiple spectral libraries that were both generated in house and purchased from outside vendors. The untargeted analysis provides information for compounds identified using accurate mass and MS/MS fragmentation spectra. Based off this analysis, clonidine was identified as being unexpectedly present in the urine.

Discussion and Conclusion: The initial patient presentation corresponded to a toxidrome consistent with alpha-2 adrenergic agonist toxicity. However, the presenting symptoms are nonspecific and may mimic other conditions, especially in the absence of exposure history. The uncertainty of etiology can lead to unnecessary testing, while also missing an underlying concern of inappropriate access to medications by children. The untargeted analysis was able to identify the presence of clonidine using accurate mass and MS/MS fragmentation patterns, however this result was presumptive given that the library entry was not generated in our library. Confirmatory analysis for clonidine was sent out to a reference laboratory and the result filed into the electronic medical record. Toxicology contacted the patient’s pediatrician with final results as the etiology of the presentation.

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