The study of degradation products of chlorpromazine hydrochloride by the method of liquid-mass spectroscopy in drugs for injection
The analysis of model samples of the drug Aminazin has been performed, its active substance is chlorpromazine hydrochloride. These model solutions were subjected to sterilization with previous exposure at room temperature. It has been found that depending on duration of the exposure during sterilization the degradation of the drug occurs in two possible ways – with formation of opalescence or without it. The schemes of degradation with formation of either one product – chlorpromazine sulfoxide, or some products – chlorpromazine sulfoxide, chlorpromazine N-oxide, nor-chlorpromazine and others have been proposed. It has been found that opalescence of solutions is caused by formation of degradation products – chlorpromazine N-oxide and norchlorpromazine that are slightly soluble in water. The analysis of model samples was performed using the liquid chromatography/mass spectrometry methods developed by the authors. In the course of analysis the molecular weights corresponding to the abovementioned products were obtained. Therefore, the experimental confirmation of the chemes of degradation proposed has been obtained. As the result of the research conducted the chromatographic method for detection of impurities using liquid chromatography/mass spectrometry has been developed, and the main ways of degradation of chlorpromazine hydrochloride in aqueous solutions have been determined. According to the result of the research the recommendations to the manufacturing process have been developed, and measures for optimizing the composition of the drug have been proposed.
European Pharmacopoeia – 8th ed. – Strasbourg: European Directorate for the Quality of Medicines, Council of Europe, 2013, 3655 p.
The United State Pharmacopeia: 37 – NF32, Rockville: The United State Pharmacopeia, Inc., 2014, 3503 p.
Derzhavna Pharmakopeia Ukraini (Ukrainian State Pharmakopoeia) / Derzhavne pidpriemstvo “Naukovo-ekspertnii pharmakopeinii centr”, Dopovnennia 2, Kharkiv: RIREG, 2008, 608 p.
Derzhavna Pharmakopeia Ukraini 1 vidannia (Ukrainian State Pharmakopoeia 1st ed.) / Derzhavne pidpriemstvo “Naukovo-ekspertnii pharmakopeinii centr”, Kharkiv: RIREG, 2008, 556 p.
McNaught A. D., Wilkinson A. Compendium of Chemical Terminology. IUPAC – 2nd ed. (the “Gold Book”), Oxford: Blackwell Scientific Publications, 2002.
Vershinin V. I., Derendiayev B. G., Lebedev K. S. Computernaia identifikacia organicheskih soedinenii (Computer identification of organic compounds), Moskow: Akademkniga, 2002, 197 p.
Currie L. A. Nomenclature in evaluation of analytical methods including detection and quantification capabilities (IUPAC Recommendations 1995). Pure Appl. Chem., 1995, Vol. 67, No.10, pp.1699-1723.
Shetti P., Venkatachalam A. LС-MS/MS Determination of Trihexaphenydyl HCl, Trifluoperazine HCl and Chlorpromazine HCl from blood plasma. Jornal of Pharmaceutical and Biomedical Sciences, 2011, Vol. 9, pp.1-10.
GOST Style Citations
This work is licensed under a Creative Commons Attribution 4.0 International License.
Abbreviated key title: Ž. org. farm. hìm.
ISSN 2518-1548 (Online), ISSN 2308-8303 (Print)