Deproteinization with ZnSO4–Ba(OH)2 reduces the photodegradation of montelukast during plasma sample preparation for HPLC analysis

Montelukast (MKT), a leukotriene receptor antagonist, degrades when it is exposed to light. The analysis of MKT content in blood plasma by high-pressure liquid chromatography requires several sample preparation steps including deproteinization. This study aimed to evaluate MKT photodegradation in blood plasma samples and optimize a deproteinization method to reduce MKT photodegradation, and thereby improve analytical quality. We evaluated the stability of MKT in water and plasma in real time using high-pressure liquid chromatography and optimized a sample deproteinization procedure by comparing the effectiveness of several deproteinization methods. When exposed to light, MKT photodegraded quickly. Although MKT photodegradation was slightly slower than that in water, a half portion (55%) of the MKT in plasma degraded within 2 h when exposed to light. The rate of MKT photodegradation was dramatically reduced by sample deproteinization using ZnSO₄–Ba(OH)₂, but it was accelerated by deproteinization through precipitation using methanol or acetonitrile. These results suggest that precautions should be taken when preparing plasma samples for the analysis of MKT, and that deproteinization of such samples using ZnSO₄–Ba(OH)₂ can reduce the risk of analytical error arising from MKT photodegradation.