Stability-indicating LC method for the quantification of Midazolam active pharmaceutical ingredient and in pharmaceutical formulations
DOI:
https://doi.org/10.22456/2527-2616.86375Keywords:
Forced degradation, HPLC, Injections, Quality control, Stress test, TabletsAbstract
A stability-indicating LC method was validated for the quantification of midazolam (MDZ) active pharmaceutical ingredient (API) and in pharmaceutical formulations. Isocratic chromatography was performed on C18 column with mobile phase containing methanol/acetonitrile/water (45:35:20 v/v/v) with 0.4% of triethylamine pH 6.5. The validation included specificity, linearity, accuracy, precision and robustness. In specificity, after acid, basic, neutral, oxidant and thermal degradation, it was found that the concentration of MDZ decreased substantially, with the appearance of peaks representatives of the degradation products, proving the stability-indicating power of the method. The response was linear in the range 50.0 – 250.0 µg.mL-1, with 11.73 µg.mL-1 and 3.87 µg.mL-1 as LOQ and LOD, respectively. Recoveries ranged between 98.68 and 100.41%. The relative standard deviation values for intra and interday precision were 1.11%, 0.82% and 1.47%, respectively. The tablets and injections containing MDZ were approved in the assay and content uniformity. The method can be adopted by pharmacopeias and for routine quality control for analysis of MDZ API, tablets and injection.
Downloads
References
Nogueira FL, Sakata RK. Palliative sedation of the terminal patient. Brazilian Journal of Anesthesiology. 2012; p. 586–592.
Gonçalves RDR, Cruz AAV. Oral midazolam as preanesthetic medication in blepharoplasties. 2009; p. 665–668.
Noranbuena C, Yanez, J, Flores V, Puentes P, Carrasco P, Villena R. Oral ketamine and midazolam for pediatric burn patients: A prospective, randomized, double-blind study. J Pediatr Surg. 2013; 48(3):629-34.
Marçon F, Mathiron D, Pilard S, Lemaire-Hurtel AS, Duballe JM, Djedaini-Pilard F. Development and formulation of a 0.2% oral solution of midazolam containing γ-cyclodextrin. Int J Pharm. 2009; 279(2):244-50.
Shekerdemian L, Bush A, Redington A. Cardiovascular effects of intravenous midazolam after open heart surgery. Arch Dis Child, 1997; 76(1):57-61
Bolon M, Boulieu R, Flamens C, Paulus S, Bastien O. Sédation par le midazolam en réanimation: aspects pharmacologiques et phamacocinétiques. Ann Fr Anesth Reanim. 2002; 6(21):478-92
Ali SM, Upadhyay SK. Complexation study of midazolam hydrochloride with β-cyclodextrin: NMR spectroscopic study in solution. Magn Reson Chem. 2008; 7(46):676-79.
Kaartama R, Jarho P, Savolainen J, Kokki H, Lehtonen M. Determination of midazolam and 1- hydroxymidazolam from plasma by gas chromatography coupled to methane negative chemical ionization mass spectrometry after sublingual administration of midazolam. J Chromatogr B. 2011; 879(19):1668-76.
Svanstron C, Hansson GP, Svensson LD, Sennbro CJ. 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. J Pharm Biomed Anal. 2012; 25(58)71-77.
Bosch ME, Sánchez AR. Analytical Methodologies for the Determination of Midazolam in Pharmaceuticals. Chromatographia. 2015; p. 609–619.
British Pharmacopoeia. British Pharmacopoeia Commission. London: The Stationery Office, 2018. CDROM.
ICH. Validation of Analytical Procedures: Text and Methodology Q2 (R1). International Conference on Harmonization, Geneva. 2005. Available at: https://www.ich.org/fileadmin/Public_Web_Site/ICH_P roducts/Guidelines/Quality/Q2_R1/Step4/ Q2_R1 Guideline.pdf. Accessed: 10 Jan 2012.
Carstensen JT, Rhodes CT. Drug Stability: Principles and practices, 3rd ed. Dekker M. 2000.
Andersin R, Tammilehto S. Photochemical decomposition of midazolam IV. Study of pHdependent stability by high-performance liquid chromatography. Int J Pharm. 1995; 2(123):229-35.
Downloads
Published
Versions
- 11-03-2026 (3)
- 09-03-2026 (2)
- 16-12-2018 (1)
How to Cite
Issue
Section
License
Copyright (c) 2018 Drug Analytical Research
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
The Copyright holder of manuscripts published is Drug Analytical Research. Authors who publish with this journal are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
Licensing:
Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License
Users are allowed to read, download, copy, distribute, print, search, or link to the full texts of the articles, or use them for any other lawful purpose, without asking prior permission from the publisher or the author.
