Preview

Epilepsy and paroxysmal conditions

Advanced search

Chromatography-tandem MASS spectrometry (HPLC-MS/MS) for the detection of valproic acid and its metabolites in blood plasma

https://doi.org/10.17749/2077-8333.2018.10.2.035-042

Abstract

Aim: to adapt the HPLC-MS/MS technique to determining valproic acid and its metabolites in blood plasma for drug therapy monitoring.

Materials and Methods: The chromatographic assay was run using an Agilent 1260 Infinity II chromatograph with a Phenomenex synergi Fusion analytical column 4 μm-C18 2×50 mm. The mobile phase consisted of 0.1% ammonium acetate in distilled water and 0.1% ammonium acetate in methanol (10:90 v/v, 0.5 ml/min). The multiple ions monitoring (MIM) mode was used for mass- spectrometric detection of valproic acid at m/z = 143.1, with the negative ion mode. The method  was found applicable over the range from 1 mcg/ml to 200 mcg/ml of valproic acid. For the mass  spectroscopy detection of valproic acid metabolites, the multiple reaction monitoring (MRM mode)  was used. MS identifications of 2-propyl-4-pentanoil-β-О-glucuronide; 2-propyl-4-pentenoic acid,  3-hydroxy-2- propylpentanoic acid, 4-hydroxy-2-propylpentanoic acid, 2-propylglutaric acid and 3- oxo-2-propylpentanoic acid in the negative ion mode were carried out at m/z 319.2→143.2; m/z  140.1→140.1; m/z 159.1→101; m/z 159.1→123.1; m/z 173→129.1 and m/z 157.05→11,  respectively. The method was sensitive over the range from 10 ng/ml to 500 ng/ml of the tested  compounds.

Results: The developed technique allows for determining valproic acid and its metabolites in a single sample; thus, the preliminary stage of separate sample preparation can be omitted, which increases the informative value of the assay without increasing its cost.

Conclusion: This innovative methodology for the quantification of valproic acid and its metabolites in the blood plasma is expected to facilitate the individual approach to the treatment of patients with epilepsy, thereby increasing the efficacy and safety of the pharmacotherapy.

About the Authors

A. S. Malygin
Tver State Medical University
Russian Federation

4 Sovetskaya Str., Tver 170100, Russia

Resident-in-Training, Chair of Pharmacology & Clinical Pharmacology, Tver State Medical University



N. S. Popov
Tver State Medical University
Russian Federation

4 Sovetskaya Str., Tver 170100, Russia

Assistant, Chair of Pharmacy, Tver State Medical University



M. A. Demidova
Tver State Medical University
Russian Federation

4 Sovetskaya Str., Tver 170100, Russia

MD, Professor & Head, Chair of Pharmacy, Tver State Medical University. Tel.: +7(4822)53-86-55



M. N. Kudrayshova
Tver State Medical University
Russian Federation

4 Sovetskaya Str., Tver 170100, Russia

PhD (Biology), Associate Professor, Chair of Pharmacy, Tver State Medical University



References

1. Ajvazyan S. O. Epilepsiya i paroksizmal’nye sostoyaniya / Epilepsy and paroxysmal conditions (in Russian). 2010; 2 (3): 2-7.

2. Baturin V. A., Baturina M. V., Kotova A. A., Skripnyuk A. A. Kachestvennaya klinicheskaya praktika (in Russian). 2016; 1: 47-49.

3. Belousov Yu.B., Leonova M. V., Shtejnberg L. L., Tishchenkova I. F. Epilepsiya i paroksizmal’nye sostoyaniya / Epilepsy and paroxysmal conditions (in Russian). 2013; 3: 6-15.

4. Leonova M. V., Ivzhic M. A., Tishchenkova I. F. et al. Epilepsiya i paroksizmal’nye sostoyaniya / Epilepsy and paroxysmal conditions (in Russian). 2017; 9 (1): 26-34.

5. Yakunina A. V., Poverennova I. E. Epilepsiya i paroksizmal’nye sostoyaniya / Epilepsy and paroxysmal conditions (in Russian). 2016; 3: 66-73. DOI: 10.17749/2077-8333.2016.8.3.066-073.

6. The order of the Ministry of Health of the Russian Federation of 22.10.2003 № 494 “On the improvement of the activity of physicians of clinical pharmacologists” [Prikaz MZ RF ot 22.10.2003 №494 «O sovershenstvovanii deyatel’nosti vrachej klinicheskih farmakologov» (in Russian)].

7. Shnajder N. A., Dmitrenko D. V. Nevrologiya, nejropsihiatriya, psihosomatika (in Russian). 2016; 8 (2): 94-99.

8. Sztajnkrycer M. D. Valproic acid toxicity: overview and management. J Toxicol Clin Toxicol. 2002; 40 (6): 789-801.

9. Popov N. S., Malygin A. S., Demidova M. A. Sovremennye problemy nauki i obrazovaniya (in Russian). 2017; 5: URL: www.science-education.ru/ru/article/view? id=26988. Accessed: 12.03.2018.

10. Zhao M., Li G., Qiu F., Sun Y. Development and Validation of a Simple and Rapid UPLC-MS Assay for Valproic Acid and Its Comparison With Immunoassay and HPLC Methods. Ther Drug Monit. 2016; 38 (2): 246-252.

11. Wen D., Chen Z., Yang C., Liu H. et al. A rapid and simple HPLC-MS/MS method for the simultaneous quantification of valproic acid and its five metabolites in human plasma and application to study pharmacokinetic interaction in Chinese epilepsy patients. J of Pharmaceutical and Biomedical Analysis. 2018; 149 (5): 448-456.

12. Zhao M., Zhang T., Li G, Qiu F., Sun Y., Zhao L. Simultaneous Determination of Valproic Acid and Its Major Metabolites by UHPLC-MS/MS in Chinese Patients: Application to Therapeutic Drug Monitoring. J Chromatogr Sci. 2017; 55 (4): 436-444.

13. Beregovyh V. V. Validation of analytical techniques for drug manufacturers. The typical management of the enterprise for the production of medicines [Validaciya analiticheskih metodik dlya proizvoditelej lekarstv. Tipovoe rukovodstvo predpriyatiya po proizvodstvu lekarstvennyh sredstv (in Russian)]. Moscow. 2008; 18- 65.

14. Guidance for Industry: Bioanalytical method validation. US Department of Health and Human Services, Food and Drug Administration, Center for Drug Evolution and Research (CDER), US Government Printing Office, Washington, DC, 2001.

15. Upendra A., Remmel A., Remmel P. Effect of Aging on Glucuronidation of Valproic Acid in Human Liver Microsomes and the Role of UDP-Glucuronosyltransferase UGT1A4, UGT1A8, and UGT1A10. Drug Metabolism and Disposition. 2009; 37 (1): 229-236.


Review

For citations:


Malygin A.S., Popov N.S., Demidova M.A., Kudrayshova M.N. Chromatography-tandem MASS spectrometry (HPLC-MS/MS) for the detection of valproic acid and its metabolites in blood plasma. Epilepsy and paroxysmal conditions. 2018;10(2):35-42. (In Russ.) https://doi.org/10.17749/2077-8333.2018.10.2.035-042

Views: 2280


ISSN 2077-8333 (Print)
ISSN 2311-4088 (Online)