Quantitative determination of cyanoacetic acid content in teriflunomide drug substance by ion chromatography using conductivity detector

Kishore V Merusomayajula,K Rama Srinivas,T Siva Rao,Ch V Sathyendranath

doi:10.1186/s43094-021-00297-1

Kishore V Merusomayajula, K Rama Srinivas + Show 2 more

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https://doi.org/10.1186/s43094-021-00297-1

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Abstract

BackgroundThe current study focuses on the development and validation of an analytical method for quantifying cyanoacetic acid (CAA) in teriflunomide drug substance using a high-performance ion chromatography (IC) with cation suppressed conductivity detection (TFM). Water was used as the diluent for preparing the sample solution, which was injected into a standard chromatographic device with 250 mm, 4.0 mm ID, and 5.0 μm particle size Metrosep A Supp 5 Ion exchange column and a suppressed conductivity detector. At a flow rate of 0.6 mL min−1 and a temperature of 40 °C, the mobile phase was delivered in an isocratic mode.ResultsCAA and TFM had retention times of 12.78 and 15.82 min, respectively. CAA has a limit of detection (LOD) of 33 μg/g and a limit of quantification (LOQ) of 101 μg/g, respectively. For LOD and LOQ accuracy, the percentage RSD of CAA is 1.7 and 1.2, respectively. The average CAA recovery percentage was found to be between 98.6 and 100.1%. With a value of 0.9998, the calibration curve yielded an excellent linear correlation coefficient for CAA. According to the ICH guidelines, all verification parameters are within the range, indicating that the system is stable.ConclusionThe elution time and run time in the currently developed ion chromatography analytical method have been reduced, demonstrating that the method is cost-effective and generally accepted, as well as simple and functional, and can be used in routine quality control tests in the industry.

Highlights

The current study focuses on the development and validation of an analytical method for quantifying cyanoacetic acid (CAA) in teriflunomide drug substance using a high-performance ion chromatography (IC) with cation suppressed conductivity detection (TFM)
We have developed a Green Ion Chromatography technique for the determination and validation of CAA in TFM in compliance with International Council for Harmonization (ICH) and the Food and Drug Administration (FDA) guidelines [30,31,32] with a reduced run time
According to ICH [31] and FDA [32, 33], the key analytical parameters that require for validation were Accuracy, Precision, Linearity, Recovery, Limit of Detection, Limit of Quantification, and Ruggedness

Summary

Introduction

The current study focuses on the development and validation of an analytical method for quantifying cyanoacetic acid (CAA) in teriflunomide drug substance using a high-performance ion chromatography (IC) with cation suppressed conductivity detection (TFM). As far as we are aware, no IC experiments have been made to date in order to identify CAA content in TFM In this context, we have developed a Green Ion Chromatography technique for the determination and validation of CAA in TFM in compliance with ICH and the FDA guidelines [30,31,32] with a reduced run time. CAA content detection process is relatively sensitive to ion-exchange chromatography together with the analytical conductometric detector approach developed and validated that may be deployed in routine testing and reporting quality control laboratories

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