Development and validation of GLC/MS-procedure of doxylamine quantitative determination

Authors

  • L. Yu. Klimenko National University of Pharmacy, Ukraine
  • S. M. Trut National University of Pharmacy, Ukraine
  • T. A. Kostina National University of Pharmacy, Ukraine
  • S. M. Poluyan Національний фармацевтичний університет, Ukraine

DOI:

https://doi.org/10.24959/ophcj.19.974

Keywords:

doxylamine, gas-liquid chromatography, validation

Abstract

Doxylamine is a hypnotic medicine used for treatment of minor sleep disorders and is a frequent cause of poisoning.
Aim. To develop GLC/MS-procedure of doxylamine quantification and carry out step-by-step validation of
the developed procedure in the variants of the method of calibration curve, method of standard and method of additions.
Results. The chromatographic conditions have been chosen for doxylamine determination by the method of GLC with mass-spectrometry detection with temperature program changing during the analysis from 70 °C to 320 °C. Retention time for doxylamine is 14.53 min. To prove the possibility of the proposed procedure application in further analysis its validation has been carried out in the variants of the method of calibration curve, method of standard and method of additions. Such validation parameters as in process stability, linearity, accuracy, precision and limit of determination have been estimated by model solutions.
Experimental part. Conditions of chromatographic analysis: Agilent 6890N/5973N/7683; НР-5MS ∅0.25 mm × 30 m, 0.25 μm; DB-17MS ∅0.25 mm × 30 m, 0.15 μm; columns are connected sequentially through Deans switch; thermostat – 70 CºС (2 min), 45 ºС/min to 210 ºС, 6 ºС/min to 320 ºС (12.56 min); transfer line – 280 ºС; ion source – 230 ºС; quadrupole – 150 ºС; electron impact, 70eV; 40 – 750 m/z; injector – 250 ºС; splitless mode; inlet carrier gas (helium) pressure: 1st column – 26.06 psi, 2nd column – 19.30 psi.
Conclusions. New procedure of doxylamine quantitative determination by the method of GLC/MS has been developed. Its validation has been carried out and acceptability for application has been shown.

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References

  1. Moffat, A. C., Osselton, M. D., Widdop, B. (Eds.). (2011). Clarke’s analysis of drugs and poisons in pharmaceuticals, body fluids and postmortem material. Pharmaceutical Press, London, 4th ed.
  3. Helland, A., Espnes, K. A., Reimers, A., Aamo, T., Zahlsen, K., Rygnestad, T., Spigset, O. (2008). Toxicological screening of medicines and drugs of abuse in emergency cases. Tidsskrift for Den norske legeforening, 128 (1), 42–45.
  5. Robertson, H. T. (2009). Drugs associated with more suicidal ideations are also associated with more suicide attempts. PLoS One, 4 (10), 7312. https://doi.org/10.1371/journal.pone.0007312
  6. Jones, A. W. (2009). Concentration distributions of the drugs most frequently identified in post-mortem femoral blood representing all causes of death. Medicine, Science and the Law, 49 (4), 257–273. https://doi.org/10.1258/rsmmsl.49.4.257
  7. Jickells, S., Negrusz, A. (Eds.). (2008). Clarke’s analytical forensic toxicology. Pharmaceutical Press, London, Chicago.
  8. Hattori, H., Yamamoto, S., Iwata, M., Takashima, E., Yamada, T., & Suzuki, O. (1992). Determination of diphenylmethane antihistaminic drugs and their analogues in body fluids by gas chromatography with surface ionization detection. Journal of Chromatography B: Biomedical Sciences and Applications, 581(2), 213–218. https://doi.org/10.1016/0378-4347(92)80274-t
  9. Maurer, H., & Pfleger, K. (1988). Screening procedure for the detection of alkanolamine antihistamines and their metabolites in urine using computerized gas chromatography-mass spectrometry. Journal of Chromatography B: Biomedical Sciences and Applications, 428, 43–60. https://doi.org/10.1016/s0378-4347(00)83889-x
  11. Friedman, H., & Greenblatt, D. J. (1985). The Pharmacokinetics of Doxylamine: Use of Automated Gas Chromatography With Nitrogen-Phosphorus Detection. The Journal of Clinical Pharmacology, 25(6), 448–451. https://doi.org/10.1002/j.1552-4604.1985.tb02875.x
  12. Siek, T. J., & Dunn, W. A. (1993). Documentation of a Doxylamine Overdose Death: Quantitation by Standard Addition and Use of Three Instrumental Techniques. Journal of Forensic Sciences, 38(3), 713–720. https://doi.org/10.1520/jfs13460j
  13. Klimenko, L. Yu., Petyunin, G. P. (2014). Development of approaches to validation of UV-spectrophotometric methods of quantitative determination in forensic and toxicological analysis: linearity and application range. Farmatsevtychnyi chasopys, 2 (30), 46–51.
  14. Klimenko, L. Yu., Petyunin, G. P., Trut, S. M., Moroz, V. P. (2014). Aktualni pytannia farmatsevtychnoi i medychnoi nauky ta praktyky, 2 (15), 15–22.
  15. Klimenko, L. Yu., Trut, S. M., Petyunin, G. P., Kostina, T. A. (2014). Determining accuracy in validation of UV-spectrophotometric methods of quantitative measurement in forensic toxicological analysis. Ukraïns’kij bìofarmacevtičnij žurnal, 2 (31), 55–67.
  16. Klimenko, L. Yu., Trut, S. M., Mykytenko, O. Ye. (2014). Approaches to determination of precision for UV-spectrophotometric methods of quantitative determination in forensic and toxicological analysis. Farmatsyia Kazakhstana, 3 (154), 44–48.
  17. Klimenko, L. Yu. (2014). Farmatsyia Kazakhstana, 4 (155), 31–35.
  18. Klimenko, L. Yu. (2014). Determination of linearity, accuracy and precision of UV-spectrophotometric methods of quantitative determination in forensic and toxicological analysis in the variant of the method of additions. Farmatsyia Kazakhstana, 7 (158), 51–58.
  19. Klimenko, L. Yu. (2015). Kompleksnyi pidkhid do rozrobky ta validatsii metodyk kilkisnoho vyznachennia analitiv u biolohichnykh ridynakh v khimiko-toksykolohichnomu analizi. Doctor’s thesis. Kharkiv, 816.
  20. Grizodub, A. I. (2016). Standartizovannye protcedury validatcii metodik kontrolia kachestva lekarstvennykh sredstv. Kharkiv: DP «Ukrainskii naukovii farmakopeinii tcentr yakosti likarskikh zasobiv», 396.

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Published

2019-06-14

How to Cite

(1)
Klimenko, L. Y.; Trut, S. M.; Kostina, T. A.; Poluyan, S. M. Development and Validation of GLC/MS-Procedure of Doxylamine Quantitative Determination. J. Org. Pharm. Chem. 2019, 17, 52-62.

Issue

Vol. 17 No. 2(66) (2019)

Section

Original Researches

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