Intrinsic Stability Study and Forced Degradation Profiling of Olopatadine hydrochloride by RP-HPLC-DAD-HRMS Method

INTRODUCTION: The forced degradation determine the intrinsic stability of the molecule by establishing degradation pathways in order to identify the likely degradation products. The objective of present research work was to establish intrinsic stability and forced degradation profiling of olopatadine hydrochloride.
METHODS: The intrinsic stability of olopatadine hydrochloride has been evaluated by RP-HPLC method, where the mixture of 0.1% formic acid and organic phase (methanol: acetonitrile; 50: 50 % v/v) was used as mobile phase at 1.0 mL/min in gradient mode. Different stress conditions have been employed to explore the intrinsic stability of olopatadine hydrochloride.
RESULTS: In acidic condition, five degradation products (DPs) viz. OLO1, OLO2, OLO3, OLO4 and OLO5 were observed. OLO5 was major DP which was increased with time and peak area of OLO was decreased. In addition to OLO3 and OLO5; two more DPs were observed in alkaline condition viz. OLO6, and OLO7 in alkaline condition. OLO5 and OLO6 were two major DPs; OLO5 was increased with time while OLO6 has zig-zag pattern of peak area with time. All DPs of neutral condition were also found in acidic condition while OLO3 and OLO5 were common in all three type of hydrolytic degradation.
DISCUSSION AND CONCLUSION: Thus, OLO has similar pattern of degradation profiling in all hydrolytic conditions (acidic, alkaline and neutral). No degradation was found in thermal, UV light and oxidative conditions for ten days. OLO-Imp was recognized as analogue structure of OLO and proposed as 11 - [(3-dimethylamino)- propylidene] - 6, 11-dihydro-dibenz[b,e]oxepin-2-propanoic acid in standard drug. OLO1 was identified as (2-(4-(dimethylamino)butyl) phenyl)methanol which may be formed by cleavage of tricyclic ring in neutral condition.