Development and validation of a stability-indicating LC-UV and LC-MS/MS methods for quantitative analysis of anisomycin and identification of degradation products

Abstract

Multifunctional drug anisomycin was subjected to forced degradation in accordance with International Conference on Harmonisation (ICH) guidelines for the first time. The drug was exposed to the recommended stress conditions of hydrolysis (acidic, alkaline and neutral), oxidation, thermal stress and photolysis, in order to investigate its stability. Optimized LC-MS/MS method was validated as recommended by ICH Q2(R1) guideline with respect to the specificity, accuracy, precision, limits of detection and quantitation, linearity and robustness. Anisomycin exhibited high instability under alkaline and thermal (neutral hydrolysis) conditions. It showed moderate stability under acidic, neutral, oxidative, thermal (acidic hydrolysis) and photolytic conditions, with the lowest degradation level observed in the case of light and oxidation stress. Formation of the same degradation product, identified as deacetylanisomycin, was observed under all applied stress conditions.

Method Development and Application of an Accelerated Solution Stability Screen for Drug Discovery

“…This validated, automated method provides data more rapidly and with good reproducibility, comparing favorably with other reported protocols. [13][14][15][16][17][18][19][20][21][22][23][24][25] The improvements to the method described herein offer higher throughput and excellent reproducibility and incorporate UV and MS detection by default. This higher throughput means the screen can be offered at an earlier stage of drug development and for more compounds, contributing earlier to attrition reduction and reducing the need 14 Pain killer Cyclopenthiazide Hypertension a The instability of omeprazole at low pH is expected from its mode of action.…”

“…This validated, automated method provides data more rapidly and with good reproducibility, comparing favorably with other reported protocols. 13–25…”

Choices of chromatographic methods as stability indicating assays for pharmaceutical products: A review

“…LC-MS had been applied as stability indicating assays in numerous studies ( Tolić et al., 2018 ). Some studies utilised HPLC in method development followed by LC-MS for compound identification.…”