Nitroglycerin: Qualitative and quantitative analysis (A review)

Abstract

Drugs containing nitrocompounds are frequently administered to patients suffering from cardiovascular disorders [1 -3]. In particular, nitroglycerin (I) is still widely used for the treatment of ischemic heart disease. This drug is available in various medicinal forms, including 0.0005 g tablets, 0.0005 and 0.001 g capsules (1% solution in oil), 1% ethanol solution, concentrated (1, 4, and 5 mg/ml) preparations for infusion, aerosols for sublingual administration (400 mg/dose), 2% ointment, and transdermal therapeutic systems.In the pure form, nitroglycerin (1,2,3-propanetrioltrinitrate) is a colorless oily liquid, which is also known as a dangerous explosive. Nitroglycerin is readily soluble in acetone, benzene, ether, methanol, acetic acid; it is also sparingly soluble in other alcohols, and poorly soluble in glycerol and water [4,5]. Being an ester, nitroglycerin possesses typical properties inherent in this class of compounds. At room temperature, nitroglycerin is stable in neutral media at pH 7.4, but decomposes in acid and alkaline media. At elevated temperatures, the rate of decomposition significantly increases [4 -6].Ready-to-use medicinal forms of nitroglycerin may contain impurities corresponding to the process of synthesis and the conditions of storage. The typical impurities are glycerin, nitrate and nitrite ions, di-and mononitroglycerins, ethylene glycol, diethylene glycol dinitrate, and others [7 -11].The broad range of possible concentrations of nitroglycerin and the possible presence of various impurities in the ready-to-use preparations necessitates the use of various methods for the analysis of these substances. The present review gives a summary of methods used for the analysis of nitroglycerin in the ready-to-use preparations currently available on the market. QUALITATIVE ANALYSIS OF NITROGLYCERINAccording to the State Pharmacopoeia (RSP-X) [12], nitroglycerin is identified using two qualitative reactions: alkaline hydrolysis (followed by the formation of acrolein) and a characteristic reaction for nitrates with diphenylamine.Foreign impurities in the ready-to-use preparations have to be determined by TLC and by paper chromatography. According to the pharmacopoeial articles for various particular ready-to-use preparations of nitroglycerin [9], foreign impurities are determined by TLC on Silufol or ATSKh plates with phosphor, which are eluted in toluene or a mixture of benzene, carbon tetrachloride, and dichloroethane (5 : 3 : 2). The spots are detected with the aid of a diphenylamine solution in chloroform and UV irradiation at 254 nm. Admitted impurities are diethylene glycol dinitrate, dinitroglycerin, and mononitroglycerin, at a total amount not exceeding 2%.It was also suggested to use TLC on silica gel plates eluted with tetrachloromethane, chloroform, ether, or the following mixtures: chloroform -ether (70 : 30) [13, 14]; chloroform -toluene (85 : 15) [7, 15]; tetrachloromethane -ether (1 : 1); tetrachloromethane -acetone (8 : 2), and tetrachloromethane -ethyl acetate (2 : 1) [16], ben...

Low hazard small-scale synthesis and chemical analysis of high purity nitroglycerine (NG)

“…20,21 Some published infrared spectra exist but most of these are historic and lack the sensitivity of modern instrumentation. 13,22,23 Historically many analytical methods, both quantitative and qualitative have been used, 24 but the most common technique for quantitative analysis is HPLC. 25,26 There are, in fact, multiple HPLC methods and procedures that have been developed by the pharmaceutical 27,28 and forensic elds 29,30 however commercial NG is expensive and is only available in small quantities (typically tens of milligrams).…”