Determination of dantrolene sodium in the presence of its process-related impurity by high-performance thin-layer chromatography—spectrodensitometry

Dantrolene sodium (DAN) is widely used as a muscle relaxant drug for the treatment of malignant hyperthermia. 5-(4-Nitrophenyl)-2-furaldehyde is reported to be DAN-related compound C (DC), and it is the synthetic precursor of DAN that may be presented as process-related impurity in a pharmaceutical formulation. Also, it is considered to be the acidic and photolytic degradation product of DAN. The synthesis of DC has been performed from p-nitroaniline with good yield and high purity; structure elucidation has been confirmed by infrared (IR), mass spectrometry (MS), and nuclear magnetic resonance (NMR) analyses. In the present study, high-performance thin-layer chromatography (HPTLC) technique was developed and validated for the separation and quantification of DAN along with DC. Separation was carried out on HPTLC silica gel 60 F254plates using a developing system consisting of chloroform—ethylacetate—acetic acid (10:0.5:0.01, by volume) with ultraviolet (UV) scanning at 380 nm. The method was highly sensitive and could be used for the determination of DAN and DC in the range of 0.1–1.5 μg band−1and 0.1–2.0 μg band−1, respectively. The method has been validated in compliance with the International Conference on Harmonization (ICH) guidelines and was successfully applied to a pharmaceutical formulation. The method was compared favorably with the reported British Pharmacopoeia high-performance liquid chromatography (BP HPLC) method.