Concentration of voxelotor in sickle cell disease can be estimated using electrophoresis and high-performance liquid chromatography.

Autor:	Curtis SA; Montefiore Medical Center, Bronx, NY, US., Friedman E; Albert Einstein College of Medicine, Bronx, NY, US., Minniti C; Montefiore Medical Center, Bronx, NY, US., Nguyen Dang A; Global Blood Therapeutics, San Francisco, CA, US., Pochron M; Global Blood Therapeutics, San Francisco, CA, US., Thomas M; Montefiore Medical Center, Bronx, NY, US., Betancourt J; Montefiore Medical Center, Bronx, NY, US., Vattappally L; Montefiore Medical Center, Bronx, NY, US., Crouch A; Montefiore Medical Center, Bronx, NY, US., Morales J; Montefiore Medical Center, Bronx, NY, US., Campbell ST; Montefiore Medical Center, Bronx, NY, US.
Jazyk:	angličtina
Zdroj:	American journal of clinical pathology [Am J Clin Pathol] 2024 Sep 03; Vol. 162 (3), pp. 297-301.
DOI:	10.1093/ajcp/aqae042
Abstrakt:	Objectives: Voxelotor can increase hemoglobin levels in patients living with sickle cell disease (SCD). A clinician who is monitoring voxelotor response may want to know whole-blood voxelotor concentration, but this cannot be measured in most clinical settings. However, voxelotor has been demonstrated to cause "peak splitting" in common methods of hemoglobin measurement such as capillary zone electrophoresis (CZE) and high-performance liquid chromatography (HPLC). We hypothesized that we could use the size of the peak split to estimate the whole-blood concentration. Methods: Blood from people with SCD was dosed with known concentrations of voxelotor, and multiparameter regression was used to derive the relationship of voxelotor concentration to the degree of peak splitting observed. To validate these equations, 21 patients started on voxelotor at 1500 mg/d had blood samples drawn at days 0, 14, 30, and 60. Samples were sent out for gold standard voxelotor concentration testing. The derived equations were then used to calculate voxelotor concentration. Results: Calculated concentrations correlated strongly with measured concentrations for both CZE (R2 = 0.83, P < .001) and HPLC (R2 = 0.76, P < .001). Voxelotor concentration also had a significant effect on increases in hemoglobin (R2 = 0.40, P < .001). Conclusions: Thus, peak splitting CZE and HPLC can be used to estimate voxelotor concentration. (© The Author(s) 2024. Published by Oxford University Press on behalf of American Society for Clinical Pathology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)
Databáze:	MEDLINE
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