Journal of Pharmaceutical and Biomedical Analysis 16 (1997) 425–429 Gas chromatography-mass spectrometry determination of isosorbide 5-mononitrate and related impurities in raw materials and dosage formulations Valentina D. Marinkovic ´ a , Smiljana S. Milojkovic ´ b , Jovan M. Nedeljkovic ´ b , Joz  ef J. C  omor b, *, Danica Agbaba c , Dobrila Z  ivanov-Stakic ´ c a Zdralje Pharmaceutical and Chemical Industry, Quality Control Sector, 16000 Leskoac, Yugoslaia b Vinc  a Institute of Nuclear Sciences, PO Box 522, 11001 Belgrade, Yugoslaia c Faculty of Pharmacy, Department of Pharmaceutical Chemistry, PO Box 146, 11000 Belgrade, Yugoslaia Received 9 December 1996; received in revised form 5 March 1997 Abstract A straightforward quantitative method for gas chromatography-mass spectrometry determination of isosorbide 5-mononitrate (IS5MN) and its related impurities such as isosorbide (IS), isosorbide diacetate (ISDA) and isosorbide 2-acetate-5-nitrate (IS2A5N) in raw materials as well as in dosage formulations is developed. The recovery of these materials was found to be 100.4 2.4, 99.3 4.7, 97.8 5.2 and 100.1 3.1%, while the detection limits were 27.2, 1.26, 1.02 and 0.78 g in dosage formulations for IS5MN, ISDA, IS2A5N, and IS, respectively. The applicability of the method was tested by analysing three different formulations of IS5MN. © 1997 Elsevier Science B.V. Keywords: Isosorbide; Isosorbide 5-mononitrate; Isosorbide diacetate; Isosorbide-2-acetate-5-nitrate; Gas chromatog- raphy-mass spectrometry; Quality control 1. Introduction Isosorbide 5-mononitrate (IS5MN) is the main metabolite of isosorbide dinitrate (ISDN) and is frequently used for treatment and prevention of angina pectoris. IS5MN has the typical pharma- codynamic action of organic nitrates, but pos- sesses a better pharmacokinetic profile, assuring enhanced biological availability. For this reason, IS5MN is nowadays more frequently used as a coronary vasodilator in various dosage formula- tions than ISDN. IS5MN has been the subject of many analytical investigations, concerning its determination as the main component of dosage formulations by col- orimetry [1], polarography [2,3], HPLC [4 – 6], GC [7,8], and TLC [4], and as a degradation product of ISDN [9–11]. Recently its stability has been investigated by capillary gas chromatography- mass spectrometry (GC-MS) [12]. Pharmacoki- netic studies of IS5MN, both as the main compound and as an active metabolite of ISDN, * Corresponding author. 0731-7085/97/$17.00 © 1997 Elsevier Science B.V. All rights reserved. PII S0731-7085(97)00079-4