Kinetic Analysis on Decomposition of Pentaerythrityl Tetranitrate under Influence of Thiols

Abstract

Pentaerythrityl tetranitrate (PETN) is an organic nitrate compound used in the therapy asgeneral vasodilator in the treatment of angina pectoris. PETN acts as prodrug for nitric oxideas active component. However, in clinical association, it is known a decreased ability oforganic nitrate to do chemical reduction, which is metabolic tolerance, by upregulation inendogenic thiol system. It has been proved that supplementation of thiol is able to overcometolerance to nitrate, nevertheless there is no comprehensive reports on interaction betweenorganic nitrate and thiol compounds. The goal of this research is to study decompositionreaction kinetic of PETN under influence N-acetyl cysteine (NAC) and thiosalicylic acid(TSA) as thiol compounds, in the physiological condition. PETN as tracing compound weremonitored by chromatographic system, with ratio of thiols used was equal, doubled, fivetimes, and ten times folds. Data were analyzed kinetically by using math equation for reactionorder 1, 2, and composite order 1 (equivalence). The result showed the linearity values onkinetic derivative, where correlation coefficient, r, is higher than 0.9 (r ≥ 0.9) for compositeorder 1. The result will give scientific contribution about tolerance phenomena in organicnitrate, particularly in the role of thiol compound to overcome nitrate tolerance.