Impurity Profiling of Baclofen Using Gradient HPLC\u2013UV Method

Adrian Leistner,Ulrike Holzgrabe

doi:10.1007/s10337-021-04079-y

Adrian Leistner, Ulrike Holzgrabe

Open Access

https://doi.org/10.1007/s10337-021-04079-y

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Journal: Chromatographia	Publication Date: Aug 13, 2021
Citations: 2	License type: open-access

Affiliation: University of Würzburg

Abstract

The GABAB receptor agonist baclofen is a medication commonly used for the treatment of muscle spasticity. It is an amino acid and related to the neurotransmitter GABA. In this study, we developed a new, gradient high-performance liquid chromatography (HPLC) method for the impurity assessment of baclofen, which is appropriate for pharmacopoeial purposes. Since the impurities related to the synthesis pathway are acids, zwitterionic, or neutral, the method development is challenging. However, the separation of all components was achieved on a C18 stationary phase using a water–acetonitrile–trifluoroacetic acid gradient. A limit of detection (LOD) of at least 0.02% was registered for all specified impurities. Additionally, CAD detection was performed to detect potential impurities lacking off a chromophore. The baclofen batches analyzed are far more pure than expected. All impurities were found below the specification limit, and thus, they can be regarded as unspecified. Moreover, the required runtime could be significantly reduced compared to the current USP or Ph. Eur. method.

Highlights

Baclofen (Fig. 1) is widely used for the treatment of muscle spasticity often occurring with multiple sclerosis, degenerative traumatic spinal cord diseases, and paraplegic syndromes [1]
Due to its structural similarity to the neurotransmitter γ-aminobutyric acid (GABA), baclofen is an agonist at the GABAB receptor in the spinal cord acting as muscle relaxant [3]
The major pharmacopoeias are not harmonized with regard to the related substances test of baclofen

Summary

Introduction

Baclofen (Fig. 1) is widely used for the treatment of muscle spasticity often occurring with multiple sclerosis, degenerative traumatic spinal cord diseases, and paraplegic syndromes [1]. Baclofen is today off-label used to treat alcoholism [2]. Due to its structural similarity to the neurotransmitter γ-aminobutyric acid (GABA), baclofen is an agonist at the GABAB receptor in the spinal cord acting as muscle relaxant [3]. Since most of the impurities of an API are productionrelated, the synthesis pathways [3, 6,7,8] have to be studied carefully to identify potential impurities.

Methods

Results

Conclusion