AQbD-Driven RP-HPLC Method for Rapid Dissolution Monitoring of Amiodarone Hydrochloride Tablets Without Sample Dilution.

Background/

Objectives

In this study, a novel reversed-phase high-performance liquid chromatography (RP-HPLC) method was established for the quality control of amiodarone hydrochloride, overcoming the limitations of the legacy compendial protocol. The conventional United States Pharmacopeia method requires a 10-fold sample dilution to avoid column overload and matrix interference from polysorbate 80. Attempting direct injection under conventional conditions severely compromises data reliability, leading to severe band broadening and peak distortion.

Methods

To fairly evaluate the intrinsic separation capacity of the analytical systems, preliminary experiments were conducted using identical, undiluted dissolution samples. Through precise chromatographic redesign, the novel method eliminates the pre-treatment dilution step. Furthermore, the reliability, precision, and robustness of the proposed method were comprehensively validated in strict accordance with the International Council for Harmonisation Q2 guidelines.

Results

Even upon direct injection of highly concentrated samples, the optimized system focuses broad peaks into sharp, symmetric, and narrow bands, increasing analytical sensitivity and theoretical plates. Furthermore, it maximizes intra-column separation efficiency, achieving complete baseline isolation of amiodarone from surfactant interferences within a retention time of approximately 6.6 min, thereby significantly improving analytical throughput.

Conclusions

By eliminating cumbersome sample preparation, minimizing analysis time, and enhancing quantitative integrity, this validated RP-HPLC method offers an efficient, high-throughput standard analytical platform. It is highly suitable for rapid routine quality control and high-precision dissolution testing of generic amiodarone pharmaceuticals in industrial settings.