Spectrometric Analysis of Dantrolene Sodium

Area of Science:

• Pharmacology
• Analytical Chemistry
• Drug Quality Control

Background:

• Dantrolene sodium is a direct-acting skeletal muscle relaxant used for malignant hyperthermia crises.
• The injectable formulation is administered intravenously.
• Ensuring consistent drug quality is critical for patient safety and treatment efficacy.

Purpose of the Study:

• To assess intra-lot and inter-lot variability in dantrolene sodium (Revonto™) using Fourier transform near-infrared spectrometry (FTNIR).
• To identify potential manufacturing differences impacting drug product consistency.

Main Methods:

• Fourier transform near-infrared spectrometry (FTNIR) was employed to analyze spectra from multiple vials of dantrolene sodium.
• Statistical analysis, including subcluster detection tests, was used to differentiate spectral groups.
• Spectra from 69 vials (lot 20REV01A) and a larger library of 141 vials from 4 lots were analyzed.

Main Results:

• Analysis of lot 20REV01A revealed two distinct spectral groups, significantly separated (66.7 SDs), suggesting different manufacturing origins.
• A broader analysis of 141 dantrolene sodium vials across 4 lots identified three separate spectral groups.
• These findings indicate that different vials may contain measurably different materials.

Conclusions:

• Significant spectral variability exists within and between lots of dantrolene sodium.
• The observed grouping suggests potential inconsistencies in the manufacturing process.
• Further investigation is warranted to understand the clinical implications of this variability for malignant hyperthermia crisis management.