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Cited by 45Analytical Methods in PharmaceuticalsForensic Toxicology and Drug AnalysisSystemic Lupus Erythematosus Research

A rapid and reliable method for the quantitation of hydroxychloroquine in serum using turbulent flow liquid chromatography-tandem mass spectrometry

Füzéry, Anna K., Breaud, Autumn R., Emezienna, Nkechinyere, Schools, Sabitha, Clarke, William A.·2013·Clinica Chimica Acta
DOI 10.1016/j.cca.2013.02.018
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Abstract

Background Hydroxychloroquine is routinely used in managing systemic lupus erythematosus and rheumatoid arthritis. Whole blood levels are currently measured in the laboratory but at least one study suggests that serum levels may be equally useful. Moreover, serum samples are the preferred matrix type in the clinical laboratory as a result of their reduced complexity compared to whole blood. These observations suggest that the clinical utility of serum hydroxychloroquine levels needs to be reevaluated using larger studies and more robust assays. We report a turbulent flow LC-MS/MS method we developed for this purpose.Methods After protein precipitation from serum with 0.33 mol/l perchloric acid, hydroxychloroquine and its deuterated analog were injected onto a Cyclone turbulent flow column for sample cleanup. Analytical separation was accomplished on a HypersilGold C8 column with a gradient of water and methanol, each containing 0.1% formic acid and 10 mmol/l ammonium formate. Analytes were ionized and detected by electrospray ionization mass spectrometry with multiple reaction monitoring.Results Our method was linear from 15.7 to 2000 ng/ml. Total imprecision at multiple levels was <5% and accuracy was within ±15%. The method showed minimal carryover. Our extraction efficiency was 103% and the matrix factor was 101%. Comparison with a reference laboratory method identified constant bias but good correlation between the 2 methods.Conclusions We present a novel turbulent flow liquid chromatography-tandem mass spectrometry method for quantification of hydroxychloroquine in serum. Our method has comparable sensitivity, selectivity, precision, accuracy, and linearity to previously reported methods. However, it offers simpler sample processing, shorter overall analysis time, and minimal carryover. These characteristics make our method well-suited for efficient analysis of the large number of samples necessary for studies on the clinical utility of serum HQ levels.

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  • Hydroxychloroquine levels were measured from EDTA whole blood using liquid chromatography-tandem mass spectrometry, with linearity from 16 to 4000 ng/mL and a coefficient of variation below 3%.

    “Hydroxychloroquine levels were quantified from EDTA whole blood by liquid chromatography-tandem mass spectrometry as described by Chambliss et al, with measurements being linear over a range of 16 to 4000 ng/mL (29). The coefficient of variation was <3%.”

    From Association of Higher Hydroxychloroquine Blood Levels With Reduced Thrombosis Risk in Systemic Lupus Erythematosus (2021) · cites this paper as [29]

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Authors
Füzéry, A. K., Breaud, A. R., Emezienna, N., Schools, S., & Clarke, W. A.
Affiliations
Johns Hopkins University (US)
Corresponding author
Clarke, William A.
ORCID
Venue
Clinica Chimica Acta
Publisher
Elsevier BV
Published
2013-06
Volume
421
Pages
79-84
ISSN
0009-8981 (ISSN-L)
DOI
10.1016/j.cca.2013.02.018
OpenAlex
W2033223023
Cited by
45
References
22
Citations by year
2025: 2 · 2024: 4 · 2023: 2 · 2022: 3 · 2021: 6 · 2020: 9 · 2019: 5 · 2018: 1 · 2017: 2 · 2016: 2 · 2015: 5 · 2014: 3 · 2013: 1
FWCI
3.49
Type
journal article
Language
en
Open access
closed
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Clinica Chimica Acta (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Physical Sciences › Chemistry › Analytical Chemistry › Analytical Methods in Pharmaceuticals
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Toxicology › Forensic Toxicology and Drug Analysis
  • Health Sciences › Medicine › Rheumatology › Systemic Lupus Erythematosus Research
Keywords
hydroxychloroquine, serum drug concentration, therapeutic drug monitoring, tandem mass spectrometry, deuterated internal standards, systemic lupus erythematosus, rheumatoid arthritis, sample cleanup, carryover
MeSH terms
Chromatography, Liquid, Humans, Hydroxychloroquine, Lupus Erythematosus, Systemic, Perchlorates, Chemical Precipitation, Sensitivity and Specificity, Time Factors, Spectrometry, Mass, Electrospray Ionization, Tandem Mass Spectrometry

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