DOI: https://doi.org/10.15587/2519-4852.2018.146364

Analysis of psychotropic medicines triazolam, estazolam and alprazolam mixture using high-performance liquid chromatography method

Yelyzaveta Kravchuk, Mindaugas Marksa, Augusta Zevzikoviene, Andrejus Zevzikovas

Abstract


Poisoning of benzodiazepines, particularly triazolam, estazolam and alprazolam usually is caused by consumption of the drug in bigger doses than prescribed.  So, for the fast determination of material caused poisoning, selective and effective methods of analysis are requested.

Methods. Benzodiazepines triazolam, estazolam and alprazolam, were chosen for investigation. Analysis was performed using chromatograph „Waters 2695” with a photodiode array detector (Waters 996, at wavelength 200-400 nm range),  ACE C18 (2,1 mm x 5,0 cm, 5 μm) chromatographic column, gradient eluent flow (sulfuric acid buffer 0,1% and ACN), eluent flow rate 0,1 ml/min and injection volume of 10 µl.

Results. Methodics for identification and quantification of triazolam, estazolam, alprazolam and their mixture was developed using reference solutions. Validated methodic was adapted for identification and quantification of triazolam, estazolam, alprazolam in medicinal products.

Conclusions. Selected methodic is  suitable for qualification and quantification of the medicinal preparations: ACE C18 (2,1 mm x 5,0 cm, 5 μm) chromatographic column, gradient eluent flow (sulfuric acid buffer 0,1% and ACN), eluent flow rate 0,1 ml/min, injection volume of 10 µl and diode array detector. Mixture of components has been examined and retention times have been stated as follows: alprazolam (13,216 min), estazolam (13,407 min) and triazolam (14,340 min). Retention time upon repetition of analysis have not exceeded the relative error of p <0,05 limitation.

Limits of detection of alprazolam is 0,01 µg/ml, estazolam 0,012 µg/ml, triazolam 0,020 µg/ml. Limit of quantification of alprazolam is 0, 022 µg/ml, estazolam 0, 025 µg/ml, triazolam 0, 045 µg/ml


Keywords


triazolam; estazolam; alprazolam; high-performance liquid chromatography; qualitative and quantitative determination

Full Text:

PDF

References


Medicines consumption in Lithuania (2017). Available at: http://www.vvkt.lt/Front-Page

Hobelmann, J. G., Clark, M. R.; Staats, P., Silverman, S. (Eds.) (2016). Benzodiazepines, Alcohol, and Stimulant Use in Combination with Opioid Use. Controlled Substance Management in Chronic Pain. Cham: Springer, 75–86. doi: http://doi.org/10.1007/978-3-319-30964-4_6

Galanter, M., Kleber, H. D., Brady, K. T. (Eds.) (2014). The American Psychiatric Publishing Textbook of Substance Abuse Treatment. Washington: American Psychiatric Publishing. doi: http://doi.org/10.1176/appi.books.9781615370030

Harvey, R. A., Champe, P. C., Finkel, R., Cubeddu, L. X., Clark, M. A. (Eds.) (2009). Lippincott Illustrated Reviews: Pharmacology. Lippincott Williams & Wilkins, 564.

Tsutaoka, B., Olson, K. R. (2012). Chapter 31. Benzodiazepines. Poisoning & Drug Overdose. McGraw-Hill, Available at: https://mhmedical.com/Content.aspx?bookId=391&sectionId=42069845

Fernández, P., González, C., Pena, M. T., Carro, A. M., Lorenzo, R. A. (2013). A rapid ultrasound-assisted dispersive liquid–liquid microextraction followed by ultra-performance liquid chromatography for the simultaneous determination of seven benzodiazepines in human plasma samples. Analytica Chimica Acta, 767, 88–96. doi: http://doi.org/10.1016/j.aca.2013.01.016

Mistry, K., Grinberg, N. (2005). Application of Monolithic Columns in High Performance Liquid Chromatography. Journal of Liquid Chromatography & Related Technologies, 28 (7-8), 1055–1074. doi: http://doi.org/10.1081/jlc-200052972

Moffat, A. C., Osselton, M. D., Widdop, B. (2011). Clarke‘s Analysis of Drugs and Poisons. London: Pharmaceutical Press, 2473.

Japp, M., Garthwaite, K., Geeson, A. V., Osselton, M. D. (1988). Collection of analytical data for benzodiazepines and benzophenones. Journal of Chromatography A, 439 (2), 317–339. doi: http://doi.org/10.1016/s0021-9673(01)83844-9

Mura, P., Piriou, A., Fraillon, P., Papet, Y., Reiss, D. (1987). Screening procedure for benzodiazepines in biological fluids by high-performance liquid chromatography using a rapid-scanning multichannel detector. Journal of Chromatography B: Biomedical Sciences and Applications, 416, 303–310. doi: http://doi.org/10.1016/0378-4347(87)80513-3

Theis, D. L., Bowman, P. B. (1983). Development of a liquid chromatographic method for the determination of triazolo-benzodiazepines. Journal of Chromatography A, 268, 92–98. doi: http://doi.org/10.1016/s0021-9673(01)95391-9

Flanagan, R. J., Storey, G. C. A., Bhamra, R. K., Jane, I. (1982). High performance liquid chromatographic analysis of basic drugs on silica columns using non-aqueous ionic eluents. Journal of Chromatography A, 247 (1), 15–37. doi: http://doi.org/10.1016/s0021-9673(00)84853-0

Chiarotti, M., De Giovanni, N., Fiori, A. (1986). Analysis of benzodiazepines: I. Chromatographic identification. Journal of Chromatography A, 358, 169–178. doi: http://doi.org/10.1016/s0021-9673(01)90326-7


GOST Style Citations


Medicines consumption in Lithuania. 2017. URL: http://www.vvkt.lt/Front-Page

Hobelmann J. G., Clark M. R. Benzodiazepines, Alcohol, and Stimulant Use in Combination with Opioid Use / ed. by Staats P., Silverman S. // Controlled Substance Management in Chronic Pain. Cham: Springer, 2016. P. 75–86. doi: http://doi.org/10.1007/978-3-319-30964-4_6 

The American Psychiatric Publishing Textbook of Substance Abuse Treatment / ed. by Galanter M., Kleber H. D., Brady K. T. Washington: American Psychiatric Publishing, 2014. doi: http://doi.org/10.1176/appi.books.9781615370030 

Lippincott Illustrated Reviews: Pharmacology / ed by Harvey R. A. et. al. Lippincott Williams & Wilkins, 2009. 564 p.

Tsutaoka B., Olson K. R. Chapter 31. Benzodiazepines // Poisoning & Drug Overdose. McGraw-Hill, 2012. URL: https://mhmedical.com/Content.aspx?bookId=391&sectionId=42069845

A rapid ultrasound-assisted dispersive liquid–liquid microextraction followed by ultra-performance liquid chromatography for the simultaneous determination of seven benzodiazepines in human plasma samples / Fernández P. et. al. // Analytica Chimica Acta. 2013. Vol. 767. P. 88–96. doi: http://doi.org/10.1016/j.aca.2013.01.016 

Mistry K., Grinberg N. Application of Monolithic Columns in High Performance Liquid Chromatography // Journal of Liquid Chromatography & Related Technologies. 2005. Vol. 28, Issue 7-8. P. 1055–1074. doi: http://doi.org/10.1081/jlc-200052972 

Moffat A. C., Osselton M. D., Widdop B. Clarke‘s Analysis of Drugs and Poisons. London: Pharmaceutical Press, 2011. 2473 p.

Collection of analytical data for benzodiazepines and benzophenones / Japp M. et. al. // Journal of Chromatography A. 1988. Vol. 439, Issue 2. P. 317–339. doi: http://doi.org/10.1016/s0021-9673(01)83844-9 

Screening procedure for benzodiazepines in biological fluids by high-performance liquid chromatography using a rapid-scanning multichannel detector / Mura P. et. al. // Journal of Chromatography B: Biomedical Sciences and Applications. 1987. Vol. 416. P. 303–310. doi: http://doi.org/10.1016/0378-4347(87)80513-3 

Theis D. L., Bowman P. B. Development of a liquid chromatographic method for the determination of triazolo-benzodiazepines // Journal of Chromatography A. 1983. Vol. 268. P. 92–98. doi: http://doi.org/10.1016/s0021-9673(01)95391-9 

High performance liquid chromatographic analysis of basic drugs on silica columns using non-aqueous ionic eluents / Flanagan R. J. et. al. // Journal of Chromatography A. 1982. Vol. 247, Issue 1. P. 15–37. doi: http://doi.org/10.1016/s0021-9673(00)84853-0 

Chiarotti M., De Giovanni N., Fiori A. Analysis of benzodiazepines: I. Chromatographic identification // Journal of Chromatography A. 1986. Vol. 358. P. 169–178. doi: http://doi.org/10.1016/s0021-9673(01)90326-7 







Copyright (c) 2018 Yelyzaveta Kravchuk, Mindaugas Marksa, Augusta Zevzikoviene, Andrejus Zevzikovas

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.

ISSN 2519-4852 (Online), ISSN 2519-4844 (Print)