Determination of diphenhydramine by HPLC method in biological liquids

Authors

DOI:

https://doi.org/10.15587/2519-4852.2020.210728

Keywords:

diphenhydramine hydrochloride, extraction with chloroform, analysis by HPLC method, blood, urine

Abstract

The aim of the study was to develop an algorithm for directed analysis of diphenhydramine in biological extracts from urine and blood using a unified method of HPLC research.

Materials and methods. The extraction of diphenhydramine was carried out with chloroform at pH 9.0. The extracts were purified from impurities by a combination of TLC and extraction with hexane. TLC purification and identification of diphenhydramine were carried out under optimal conditions: organic solvents systems – chloroform-methanol (90:10); methanol; methanol-25 % solution of ammonium hydroxide (100:1.5) and chromatographic plates - Sorbfil PTLC-AF-A, Sorbfil PTLC-P-B-UV. For the detection of diphenhydramine, the most sensitive location reagents were used - UV light (λ = 254 nm) and Dragendorff reagent in the modification of Mounier.

HPLC analysis was carried out on a microcolumn liquid chromatograph "Milichrome A-02" in conditions: reversed-phase variant, column with non-polar sorbent Prontosil 120-5 C18 AQ, 5 μm; mobile phase in the mode of linear gradient – from eluent А (5 % acetonitrile and 95 % buffer solution) to eluent B (100 % acetonitrile) as during 40 min. The flow rate of the mobile phase has been formed 100 μl/min, injection volume – 4 μl. Multichannel detection of the substance was carried out using a UV spectrophotometer at 210, 220, 230, 240, 250, 260, 280 and 300 nm; the optimal value of column temperature – 37 - 40°С and pressure of pump – 2.8 – 3.2 MPa.

Results and its discussion. Extraction, purification, identification and quantitative determination of diphenhydramine were carried out according to the developed methods. It is established that when isolating diphenhydramine from blood according to the developed methods it is possible to allocate 34.2 – 38.4 % of substance ( = ± 5.69 %, RSD = 2.04 %) and from urine – 55.8 – 60.5 % of substance ( = ± 3.91 %, RSD = 1.40 % ).

Conclusions. An algorithm has been developed for directed analysis of diphenhydramine in biological extracts from urine and blood using a unified HPLC method. Statistical processing of the experimental results indicates the reliability and reproducibility of the technique

Author Biographies

Оlena Mamina, National Pharmaceutical University Pushkinska str., 53, Kharkiv, Ukraine, 61002

Doctor of Pharmaceutical Sciences, Professor

Department of Physical and Colloid Chemistry

Volodimir Kabachny, National University of Pharmacy Pushkinska str., 53, Kharkiv, Ukraine, 61002

Doctor of Pharmaceutical Sciences, Professor

Department of Inorganic and Physical Chemistry

Tetyana Tomarovska, National University of Pharmacy Pushkinska str., 53, Kharkiv, Ukraine, 61002

PhD, Associate Professor

Department of Inorganic and Physical Chemistry

Natalya Bondarenko, National University of Pharmacy Pushkinska str., 53, Kharkiv, Ukraine, 61002

PhD, Associate Professor

Department of Inorganic and Physical Chemistry

References

  1. Mashkovskii, M. D. (2012). Lekarstvennye sredstva. Moscow: Novaia Volna, 1216.
  2. Luss, L. V. (2016). Choice of an antihistamine administration route in the treatment of allergic diseases. Terapevticheskii Arkhiv, 88 (3), 93–95. doi: http://doi.org/10.17116/terarkh201688393-95
  3. Sawicka, K. M., Goez, H., Huntsman, R. J. (2016). Successful Treatment of Paroxysmal Movement Disorders of Infancy With Dimenhydrinate and Diphenhydramine. Pediatric Neurology, 56, 72–75. doi: http://doi.org/10.1016/j.pediatrneurol.2015.10.019
  4. Li, Y.-Y., Zeng, Y.-S., Chen, J.-Y., Wang, K.-F., Hsing, C.-H., Wu, W.-J. et. al. (2019). Prophylactic diphenhydramine attenuates postoperative catheter-related bladder discomfort in patients undergoing gynecologic laparoscopic surgery: a randomized double-blind clinical study. Journal of Anesthesia, 34 (2), 232–237. doi: http://doi.org/10.1007/s00540-019-02724-3
  5. Pickett, L. E., Macdonald, J. (2016). Injectable Diphenhydramine Used as Anaesthetic for Wide Local Excision With Flap Closure. Journal of Cutaneous Medicine and Surgery, 21 (3), 256–257. doi: http://doi.org/10.1177/1203475416681760
  6. Drogovoz, S. M., Lukianchuk, V. D., SHerman, B. S., Kononenko A. V. (2012). Toksicheskie effekty blokatorov N1 – gistaminovykh retseptorov i mekhanizmy ikh formirovaniia. Sovremennye problemy toksikologii, 3-4, 58–59.
  7. Thomas, S. H. L. (2012). Antihistamine poisoning. Medicine, 40 (3), 109–110. doi: http://doi.org/10.1016/j.mpmed.2011.12.012
  8. Varma, A., Ford, L., Patel, N., Vale, J. A. (2017). Elimination half-life of diphenhydramine in overdose. Clinical Toxicology, 55 (6), 615–616. doi: http://doi.org/10.1080/15563650.2017.1296153
  9. Cherukuri, S. V., Purvis, A. W., Tosto, S. T., Velayati, A. (2019). IV Lipid Emulsion Infusion in the Treatment of Severe Diphenhydramine Overdose. American Journal of Case Reports, 20, 758–763. doi: http://doi.org/10.12659/ajcr.912523
  10. Namazova-Baranova, L. S. (2009). Smertnost ot antigistaminnykh preparatov pervogo pokoleniia. Pozitsiia reguliatornykh organov. Pozitsiia vracha-pediatra. Pediatricheskaia farmakologiia, 6 (3), 52.
  11. Zagorodniy, S. L., Vasyuk, S. O. (2015). Validation of quantitative determination methods of diphenhyramine tablets by high performance liquid chromatography. Zaporozhye Medical Journal, 2 (89), 89–92. doi: http://doi.org/10.14739/2310-1210.2015.2.42122
  12. Zhiliakova, E. T., Zinchenko A. A., Novikov, O. O., Popov, N. N. (2015). Razrabotka metodiki opredeleniia miramistina i dimedrola v novykh prolongirovannykh glaznykh kapliakh dlia lecheniia bakterialnykh koniuktivitov. Nauchnye vedomosti Belgorodskogo gosudarstvennogo universiteta. Seriia: Meditsina. Farmatsiia, 30 (10), 211–217.
  13. Grigorev, A. M., Mashkova, I. V., Rudakova, L. V. (2008). Opredelenie metabolitov dimedrola metodami GKH-MS i VEZHKH v moche. Sorbtsionnye i khromatograficheskie protsessy, 8 (1), 134–140.
  14. Gelotte, C. K., Zimmerman, B. A., Thompson, G. A. (2017). Single-Dose Pharmacokinetic Study of Diphenhydramine HCl in Children and Adolescents. Clinical Pharmacology in Drug Development, 7 (4), 400–407. doi: http://doi.org/10.1002/cpdd.391
  15. Krupina, N. A., Krasnova, R. R., Pashovkina, R. N. (2005). Khimiko-toksikologicheskii analiz lekarstvennykh veschestv v krovi (plazme, syvorotke) metodom vysokoeffektivnoi zhidkostnoi khromatografii. Perspektivy razvitiia i sovershenstvovaniia sudebno-meditsinskoi nauki i praktiki. Tiumen, 316.
  16. Melentev, A. B. (2002). Skrining lekarstvennykh, narkoticheskikh veschestv i ikh metabolitov metodom gazovoi khromatografii s mass-selektivnym detektorom. Problemy ekspertizy v meditsine, 2 (4), 15–20.
  17. Derzhavna Farmakopeia Ukrainy (2004). DP «Naukovo-ekspertnyi farmakopeinyi tsentr». Kharkiv: RIREH, 520.
  18. Clarke, E. J. C. (2011). Isolation and Identification of Drugs in Pharmaceuticals, Body Fluids and Postmortem Materia. London: The Pharm. Press, 2463.
  19. Tomarovskaya, T. O., Mamina, O. O., Kabachny, V. I. (2018). The choice of optimal conditions for chemical-toxicological analysis of diphenhydramine by the thin-layer chromatography. Science and Society. Hamilton, 194–200.
  20. Baram, G. I. (2005). KHromatograf «Milikhrom A–02». Opredelenie veschestv s primeneniem baz dannykh «VEZHKH–UF». Novosibirsk: ZAO Institut khromatografii, 64.
  21. Mаmina, O. O., Kabachny, V. I., Bondarenko, N. Yu. (2019). The determination of dimedrol by the HPLC method. Advances of science. Karlovy Vary – Kyiv, 91–101.

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Published

2020-08-31

How to Cite

Mamina О., Kabachny, V., Tomarovska, T., & Bondarenko, N. (2020). Determination of diphenhydramine by HPLC method in biological liquids. ScienceRise: Pharmaceutical Science, (4 (26), 18–24. https://doi.org/10.15587/2519-4852.2020.210728

Issue

No. 4 (26) (2020)

Section

Pharmaceutical Science

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Copyright (c) 2020 Оlena Mamina, Volodimir Kabachny, Tetyana Tomarovska, Natalya Bondarenko

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