THE COMPARISON OF METHODS FOR THE QUANTITATIVE DETERMINATION OF COENZYME Q10

DOI: https://doi.org/10.29296/25877313-2019-05-02
Номер журнала: 
5
Год издания: 
2019

V.I. Zozina Post-graduate Student, Department of Clinical Pharmacology and Propaedeutics of Internal Diseases, I.M. Sechenov First Moscow State Medical University (Sechenov University) E-mail: zozinavi@gmail.com E.S. Melnikov Ph.D. (Biol.), Assistant of the A.P. Arzamastsev Department of Pharmaceutical and Toxicological Chemistry, I.M. Sechenov First Moscow State Medical University (Sechenov University) L.M. Krasnykh Ph.D. (Biol.), Head of Clinical Pharmacokinetics, Clinical Pharmacology Center, FSBI «Scientific Centre for Expert Evaluation of Medicinal Products» of the Ministry of Health of the Russian Federation O.A. Goroshko Ph.D. (Pharm.), Senior Researcher, Clinical Pharmacokinetics, Clinical Pharmacology Center, FSBI «Scientific Centre for Expert Evaluation of Medicinal Products» of the Ministry of Health of the Russian Federation V.G. Kukes Academician of the RAS, Dr.Sc. (Med.), Professor, Department of Clinical Pharmacology and Propaedeutics of Internal Diseases, I.M. Sechenov First Moscow State Medical University (Sechenov University)

Background. Coenzyme Q10 is a biologically active compound that performs many important functions in the body: electron transfer in the mito-chondrial cascade of adenosine triphosphate synthesis, antioxidant, preventing lipid peroxidation. Study Objective. The aim is to develop and compare methods for the quantitative determination of coenzyme Q10 in order to identify the most sensitive, simple and reproducible one. Materials and methods. Coenzyme Q10 was determined using high performance liquid chromatography with spectrophotometric and mass spectrometric detectors. In developing the HPLC-MS / MS it was used the electrospray ionization (ESI) in positive mode. Detection was carried out in the mode of monitoring multiple reactions (MRM). Results. The study developed and validated two methods for the determination of coenzyme Q10 in plasma. It was shown that the most sensitive and reproducible technique was HPLC-MS / MS (the LLOQ constituted 0.10 µg / ml). One-step sample preparation involving proteins precipitation, used in the HPLC-MS / MS method was more convenient than in HPLC-UV one. The LLOQ of ubiquinone in the HPLC-UV method was 0.5 μg / ml. Using the HPLC-MS / MS technique, we analyzed the average concentration of endogenous CoQ10 in patients with cardiovascular pathologies administrating statins, β-blockers and calcium channel blockers, which constituted 0.39 µg / ml. Conclusion. It was concluded that the HPLC-UV method is unsuitable for routine practice use due to the high LLOQ (0.5 µg / ml) and its low sen-sitivity. While the of HPLC-MS / MS method was selective, sensitive, fast and convenient for introduction into routine practice.

Ключевые слова: 
CoQ10
ubiquinone
HPLC-UV
HPLC-MS/MS

Список литературы: 
  1. Lunetta S., Roman M. Determination of coenzyme Q10 content in raw materials and dietary supplements by high-performance liquid chromatography-UV: collaborative study // J AOAC Int. 2008; 91(4):702-8.
  2. Orozco D., Skamarack J., Reins K., et al. Determination of ubidecarenone (coenzyme Q10, ubiquinol-10) in raw materials and dietary supplements by high-performance liquid chromatography with ultraviolet detection: single-laboratory validation // J AOAC Int. 2007; 90(5):1227-36.
  3. Raitakari O.T., McCredie R.J., Witting P., et al. Coenzyme Q improves LDL resistance to ex vivo oxidation but does not enhance endothelial function in hypercholesterolemic young adults // Free Radic Biol Med. 2000; 28(7):1100-5.
  4. Cobanoglu U., Demir H., Cebi A., et al. Lipid peroxidation, DNA damage and coenzyme Q10 in lung cancer patients--markers for risk assessment? // Asian Pac J Cancer Prev. 2011; 12(6):1399-403.
  5. Michalkiewicz S. Voltammetric determination of coenzyme Q10 in pharmaceutical dosage forms // Bioelectrochemistry. 2008; 73(1): 30-6.
  6. Battino M., Girotti S., et al. Free radical scavenging activity of coenzyme 0 measured by a chemiluminescent assay // Anal Chim Acta. 1991; 255:367–71.
  7. Karpinska J., Mikoluc B., Piotrowska-Jastrzebska J. Application of derivative spectrophotometry for determination of coenzyme Q10 in pharmaceuticals and plasma // J Pharm Biomed Anal. 1998; 17(8):1345-50.
  8. Karpinska J., Mikoluc B., Motkowski R., et al. HPLC method for simultaneous determination of retinol, alpha-tocopherol and coenzyme Q10 in human plasma // J Pharm Biomed Anal. 2006; 42(2):232-6.
  9. Jiang P., Wu M., Zheng Y., et al. Analysis of coenzyme Q(10) in human plasma by column-switching liquid chromatography // J Chromatogr B Analyt Technol Biomed Life Sci. 2004; 805(2):297-301.
  10. Hansen G., Christensen P., Tuchsen E., et al. Sensitive and selective analysis of coenzyme Q10 in human serum by negative APCI LC-MS // Analyst. 2004; 129(1):45-50.
  11. Ivanov R., Sekareva G., Kravtsova O., Kudlaj D., Luk'ja-
  12. nov S., Tihonova I., Demin A., Maksumova L., Nikitina I., Obuhov A., Zajtsev D., Stepanov A., Nosyreva M., Samso-nov M. Pravila provedenija issledovanij bioanalogovyh lekarstvennyh sredstv (bioanalogov) // Farmakokinetika i farmakodinamika. 2014. № 1. S. 21–36. (Ivanov R., Sekaryova G., Kravcova O., Kudlaj D., Luk’yanov S., Tihonova I., Dyomin A., Maksumova L., Nikitina I., Obuhov A., Zajcev D., Stepanov A., Nosyreva M., Samsonov M. Pravila provedeniya issledovanij bioanalogovyh lekarstvennyh sredstv (bioanalogov) // Farmakokinetika i farmakodinamika. 2014. № 1. S. 21–36).

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