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Rapid and sensitive analysis of reduced and oxidized coenzyme Q10 in human plasma by ultra performance liquid chromatography-tandem mass spectrometry and application to studies in healthy human subjects.
Ann Clin Biochem. 2016 Mar; 53(Pt 2):265-73.AC

Abstract

BACKGROUND

Coenzyme Q10 is an endogenous antioxidant as well as a popular dietary supplement. In blood circulation, coenzyme Q10 exists predominantly as its reduced ubiquinol-10 form, which readily oxidizes to ubiquinone-10 ex vivo. Plasma concentrations of coenzyme Q10 reflect net overall metabolic demand, and the ratio of ubiquinol-10:ubiquinone-10 has been established as an important biomarker for oxidative stress. However, the lability of ubiquinol-10 makes accurate determination of both forms of coenzyme Q10 difficult. Ex vivo oxidation of ubiquinol-10 to ubiquinone-10 during sample collection, processing and analysis may obfuscate the in vivo ratio.

METHODS

We developed a rapid and sensitive method for the determination of ubiquinol-10 and ubiquinone-10 in human plasma, using coenzyme Q9 analogues as internal standards. Single-step protein precipitation in 1-propanol, a lipophilic and water-soluble alcohol, allowed for rapid extraction.

RESULTS

Analysis by ultra performance liquid chromatography-tandem mass spectrometry provided rapid run-time and high sensitivity, with lower limits of quantitation for ubiquinol-10 and ubiquinone-10 of 5 μg/L and 10 μg/L, respectively.

CONCLUSIONS

This method is suitable for clinical studies with coenzyme Q10 supplementation in various disease states where this lipid-antioxidant may be beneficial. We have applied this method to >300 plasma samples from coenzyme Q10 research studies in chronic haemodialysis patients and postsurgical patients.

Authors+Show Affiliations

Pharmacokinetics Laboratory, Department of Pharmaceutics, School of Pharmacy, University of Washington, Seattle, WA, USA.Department of Pharmacy, School of Pharmacy, University of Washington, Seattle, WA, USA Kidney Research Institute, Division of Nephrology, Department of Medicine, School of Medicine, University of Washington, Seattle, WA, USA.Pharmacokinetics Laboratory, Department of Pharmaceutics, School of Pharmacy, University of Washington, Seattle, WA, USA.Pharmacokinetics Laboratory, Department of Pharmaceutics, School of Pharmacy, University of Washington, Seattle, WA, USA.Kidney Research Institute, Division of Nephrology, Department of Medicine, School of Medicine, University of Washington, Seattle, WA, USA.Pharmacokinetics Laboratory, Department of Pharmaceutics, School of Pharmacy, University of Washington, Seattle, WA, USA Department of Pharmacy, School of Pharmacy, University of Washington, Seattle, WA, USA Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA, USA ds@uw.edu.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Validation Study

Language

eng

PubMed ID

26056391

Citation

Claessens, Adam J., et al. "Rapid and Sensitive Analysis of Reduced and Oxidized Coenzyme Q10 in Human Plasma By Ultra Performance Liquid Chromatography-tandem Mass Spectrometry and Application to Studies in Healthy Human Subjects." Annals of Clinical Biochemistry, vol. 53, no. Pt 2, 2016, pp. 265-73.
Claessens AJ, Yeung CK, Risler LJ, et al. Rapid and sensitive analysis of reduced and oxidized coenzyme Q10 in human plasma by ultra performance liquid chromatography-tandem mass spectrometry and application to studies in healthy human subjects. Ann Clin Biochem. 2016;53(Pt 2):265-73.
Claessens, A. J., Yeung, C. K., Risler, L. J., Phillips, B. R., Himmelfarb, J., & Shen, D. D. (2016). Rapid and sensitive analysis of reduced and oxidized coenzyme Q10 in human plasma by ultra performance liquid chromatography-tandem mass spectrometry and application to studies in healthy human subjects. Annals of Clinical Biochemistry, 53(Pt 2), 265-73. https://doi.org/10.1177/0004563215593097
Claessens AJ, et al. Rapid and Sensitive Analysis of Reduced and Oxidized Coenzyme Q10 in Human Plasma By Ultra Performance Liquid Chromatography-tandem Mass Spectrometry and Application to Studies in Healthy Human Subjects. Ann Clin Biochem. 2016;53(Pt 2):265-73. PubMed PMID: 26056391.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Rapid and sensitive analysis of reduced and oxidized coenzyme Q10 in human plasma by ultra performance liquid chromatography-tandem mass spectrometry and application to studies in healthy human subjects. AU - Claessens,Adam J, AU - Yeung,Catherine K, AU - Risler,Linda J, AU - Phillips,Brian R, AU - Himmelfarb,Jonathan, AU - Shen,Danny D, Y1 - 2015/06/08/ PY - 2015/06/03/accepted PY - 2017/03/01/pmc-release PY - 2015/6/10/entrez PY - 2015/6/10/pubmed PY - 2016/11/1/medline KW - UPLC-MS/MS KW - oxidized CoQ10 KW - plasma concentrations KW - reduced Coq10 KW - stability SP - 265 EP - 73 JF - Annals of clinical biochemistry JO - Ann. Clin. Biochem. VL - 53 IS - Pt 2 N2 - BACKGROUND: Coenzyme Q10 is an endogenous antioxidant as well as a popular dietary supplement. In blood circulation, coenzyme Q10 exists predominantly as its reduced ubiquinol-10 form, which readily oxidizes to ubiquinone-10 ex vivo. Plasma concentrations of coenzyme Q10 reflect net overall metabolic demand, and the ratio of ubiquinol-10:ubiquinone-10 has been established as an important biomarker for oxidative stress. However, the lability of ubiquinol-10 makes accurate determination of both forms of coenzyme Q10 difficult. Ex vivo oxidation of ubiquinol-10 to ubiquinone-10 during sample collection, processing and analysis may obfuscate the in vivo ratio. METHODS: We developed a rapid and sensitive method for the determination of ubiquinol-10 and ubiquinone-10 in human plasma, using coenzyme Q9 analogues as internal standards. Single-step protein precipitation in 1-propanol, a lipophilic and water-soluble alcohol, allowed for rapid extraction. RESULTS: Analysis by ultra performance liquid chromatography-tandem mass spectrometry provided rapid run-time and high sensitivity, with lower limits of quantitation for ubiquinol-10 and ubiquinone-10 of 5 μg/L and 10 μg/L, respectively. CONCLUSIONS: This method is suitable for clinical studies with coenzyme Q10 supplementation in various disease states where this lipid-antioxidant may be beneficial. We have applied this method to >300 plasma samples from coenzyme Q10 research studies in chronic haemodialysis patients and postsurgical patients. SN - 1758-1001 UR - https://www.unboundmedicine.com/medline/citation/26056391/Rapid_and_sensitive_analysis_of_reduced_and_oxidized_coenzyme_Q10_in_human_plasma_by_ultra_performance_liquid_chromatography_tandem_mass_spectrometry_and_application_to_studies_in_healthy_human_subjects_ L2 - http://journals.sagepub.com/doi/full/10.1177/0004563215593097?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -