A comparative study of intravenous midazolam marketed in Libya
Amal K. Belaid, Ruwida M. Kamour, Zaema A. Elbaroudi, Walid EL-Nifati EL-Fetori, Rashad A. Ghrew
Abstract
Midazolam, a benzodiazepine medication, is used for sedation during diagnostic and therapeutic medical procedures. Insufficient doses of sedatives, including midazolam, can result in patient anxiety and awareness during the procedure. Several brands of midazolam are available in the Libyan market. This study aims to identify and estimate the medication content of intravenous midazolam in various marketed products using different analytical methods. Product identity was confirmed using Infrared methods (IR) and retention times of High-Performance Liquid Chromatographic methods (HPLC). Quantification was performed using a rapid reverse-phase HPLC method. Chromatographic analysis was conducted on a C18 column (250 mm×3.3 mm I.D., 5.0 μm particle size) with a mobile phase comprising acetonitrile, methanol, and 0.065 M ammonium acetate buffer (50: 20: 30, v/v/v), adjusted to a pH of 5.5±0.02 with orthophosphoric acid, at a flow rate of 1.0 ml/min. Ultraviolet (UV) detection was set at 220 nm. The identification results met British Pharmacopeia (BP) standards. However, the midazolam content in the Tunisian brand was shallow compared to the products from Germany and Switzerland. Thus, post-marketing testing is essential to assess the quality of critical drugs like midazolam, and further investigations, including clinical evaluations and regulatory follow-up, are necessary.
Keywords
References
- Lader M (2011) Benzodiazepines revisited-will we ever learn? Addiction. 106 (12): 2086-2109. doi: 10.1111/j.1360 -0443.2011.03563.x
- Shader RI, Greenblatt DJ (1974) Benzodiazepines in clinical practice. British Journal of Clinical Pharmacology. 1 (4): 235-244. Corpus: 202809842.
- Reves JG, Fragen RJ, Vinik HR, Greenblatt DJ (1985) Midazolam: Pharmacology and uses. Anesthesiology. 62 (3): 310-324. PMID: 3156545.
- Zhou S, Zhu J, Sun X, Xie L, Zhao Y, Ding S, Wang L, Chen J, Zhu B, Zheng A, Li Y, Zhou C, Shao F (2023) Safety, pharmacokinetics, and pharmacodynamics of midazolam gel after rectal administration in healthy Chinese subjects. Clinical Drug Investigation. 43 (6): 421-433. doi: 10.1007/s40261-023-01276-5
- Peter J-U, Dieudonné P, Zolk O (2024) Pharmacokinetics, pharmacodynamics, and side effects of midazolam: A review and case example. Pharmaceuticals. 17, 473. doi: 10.3390/ph17040473
- Walser A, Benjamin LE, Flynn T, Mason C, Schwartz R, Fryer RI (1978) Quinazolines and 1,4-benzodiazepines. 84. Synthesis and reactions of imidazo[1,5-a][1,4]benzodiazepines. The Journal of Organic Chemistry. 43 (5): 936-944. doi: 10.1021/jo00399a029
- Marçon F, Mathiron D, Pilard S, Lemaire-Hurtel AS, Duballe JM, Djedaini-Pilard F (2009) Development and formulation of a 0.2% oral solution of midazolam containing γ-cyclodextrin. International Journal of Pharmaceutics. 379 (2): 244-250. doi: 10.1016/j.ijpharm.2009.05.029
- Reves JG, Fragen RJ, Vinik HR, Greenblatt DJ (1985) Midazolam: Pharmacology and uses. Anesthesiology. 62 (3): 310-324. PMID: 3156545.
- British Pharmacopoeia Commission (2008) British Pharmacopoeia. Midazolam injection. Great Britain. Illustrated revised. Her Majesty's Stationery Office. ISBN: 0113227507, 9780113227501.
- Svanstron C, Hansson GP, Svensson LD, Sennbro CJ (2012) Development and validation of a method using supported liquid extraction for the simultaneous determination of midazolam and 1-hydroxy-midazolam in human plasma by liquid chromatography with tandem mass spectrometry detection. Journal of Pharmaceutical and Biomedical Analysis. 25 (58): 71-77. doi: 10.1016/j.jpba.2011.09.015
- Bosch ME, Ruzi-Sánchez AJ, Sanchez-Rojas F, Bosch-Ojeda C (2015) Analytical methodologies for the determination of midazolam in pharmaceuticals. Chromatographia. 78 (9-10): 609-619. doi: 10.1007/s10337-015-2885-z
- British Pharmacopoeia. British Pharmacopoeia Commission. London: The Stationery Office, 2018. CDROM.
- Costa BRD, Bertol CD, Anzilaggo D, Stulzer HK, Rossato-Grando LG (2018) Stability-indicating LC method for the quantification of midazolam active pharmaceutical ingredient and in pharmaceutical formulations. Drug Analytical Research. 2 (2): 44-48. doi: 10.22456/2527-2616.86375
- ICH QA (R2) International Conference on Harmonization (2003) Stability testing of new drug substances and products-scientific guidelines. 1-20. Reference Number: CPMP/ICH/2736/99. 7 West Ferry Circus, Canary Wharf, London, E14 4HB, UK.
Submitted date:
09/12/2024
Reviewed date:
10/28/2024
Accepted date:
11/06/2024
Publication date:
11/07/2024