Analytical Methods for Imeglimin Hydrochloride: A Comprehensive Review of Current Approaches and Advances

Abstract

Imeglimin hydrochloride is a unique anti-diabetic medication that is primarily used to treat type 2 diabetes. The rising frequency of this chronic illness needs the development of effective analytical methods for precise measurement and characterisation of imeglimin hydrochloride in pharmaceutical formulations and biological systems. This comprehensive analysis investigates existing approaches and recent advances in the analytical techniques used to determine imeglimin hydrochloride. Key technologies such as high-performance liquid chromatography (HPLC), mass spectrometry (MS), spectrophotometry, and electrochemical analysis are evaluated for sensitivity, specificity, and applicability. Furthermore, the paper discusses current trends in the creation of more dependable and cost-effective procedures, such as downsized systems and the incorporation of newer technology. The review also covers advances in technique development, such as the adoption of novel stationary phases, mobile phase optimizations, and sensitivity enhancements.

Introduction

1. Background & Importance
The pharmaceutical industry is rapidly advancing analytical methods to meet rising demands in drug quality control, impurity detection, cost reduction, and faster drug development. Imeglimin hydrochloride, a first-in-class oral antidiabetic agent, is gaining attention for its unique mechanism in treating Type 2 Diabetes Mellitus (T2DM). With its increasing clinical use, there's a growing need for robust, rapid, and precise analytical and stability testing methods.

2. Pharmacological Overview

• Mechanism of Action: Imeglimin improves glucose utilization through:

  • Enhancing insulin sensitivity in the liver, muscle, and adipose tissues.

  • Amplifying glucose-stimulated insulin secretion (GSIS).

  • Preserving β-cell mass and mitochondrial function.

• Pharmacokinetics: Rapidly absorbed (Tmax ~1–2 hrs), with a 24-hour half-life, metabolized via CYP3A4, and excreted renally.

• Pharmacodynamics: Increases insulin output in response to glucose and preserves pancreatic function.

3. Clinical Use

• Approved Indications:

  • Monotherapy for patients unresponsive to diet/exercise.

  • Combination therapy with metformin, SGLT2 inhibitors, or insulin for uncontrolled blood glucose.

• Off-Label Potential: Possible use in metabolic syndrome, PCOS, and neurodegenerative diseases due to its mitochondrial effects.

4. Clinical Efficacy

• Trial Data:

  • Phase II and III trials showed reductions in HbA1c (0.5%–0.9%) and fasting plasma glucose.

  • Well tolerated with minor side effects (e.g., nausea, diarrhea).

  • Comparable to metformin in efficacy but with fewer GI side effects.

5. Dosage & Administration

• Standard dosage: 1000 mg twice daily (with or without food).

• Adjustments needed for renal impairment and elderly patients.

• Suitable for long-term use with routine monitoring.

6. Chemical & Structural Characteristics

• Key structural groups: Benzoxazole core, benzyl group, guanidine moiety.

• These contribute to its unique mitochondrial targeting and metabolic regulation, distinguishing it from other T2DM drugs.

7. Analytical Method Development

• UV-Vis Spectroscopy: For basic quantification.

• HPLC & UPLC: Widely used for precise, sensitive, and fast imeglimin analysis.

• LC-MS/MS: For accurate detection in biological matrices like plasma and urine.

• Emphasis on method validation parameters (accuracy, precision, specificity) per ICH and USFDA standards.

8. Formulation Advances

• Nanotechnology (e.g., lipid nanoparticles, nanocrystals) improves solubility and bioavailability.

• Modified-release formulations provide sustained glycemic control.

• Patient-centric approaches include combination tablets and orally disintegrating tablets (ODTs) for improved compliance.

9. Stability & Degradation Studies

• Forced degradation studies: Assess stability under stress (acidic, basic, oxidative, thermal, photolytic conditions).

• Long-term stability testing: Determines shelf-life and ensures safety and efficacy using HPLC, MS, UPLC.

• Compliant with ICH guidelines for pharmaceutical quality assurance.

10. Regulatory Considerations

• Not yet approved by the EMA or FDA.

• Undergoing clinical trials in Europe and the U.S..

• May qualify for centralized approval and potentially Orphan Drug Designation if positioned for rare indications.

Conclusion

The invention and refinement of analytical procedures for imeglimin hydrochloride have helped to ensure its purity, safety, and efficacy in clinical use. Techniques such as UV,HPLC, UPLC,MS, and spectroscopy have various advantages, including high sensitivity, adaptability, and the capacity to handle complicated biological material. These approaches are critical for drug discovery, clinical pharmacology, and real-time monitoring of Type 2 diabetic patients.However, some technologies, particularly those using multidimensionalapproaches or advanced instrumentation, continue to present cost, time, and complexity issues. Furthermore, bioanalysis in complex matrices requires careful management of potential mistakes caused by matrix effects. Despite these hazards, the ongoing improvement of analytical tools promises to resolve these limits while also improving imeglimin hydrochloride monitoring and application. In the future, the integration of emerging technologies such as portable biosensors and rapid diagnostic tools may improve imeglimin\'s real-time analysis and therapeutic monitoring, potentially revolutionizing its clinical application and contributing to the larger diabetes management landscape.

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Copyright

Copyright © 2025 Kadambari S. Wagh, Tejashri R. Dugaje, Priyanka B. Jadhav, Chetna Y. Gavit, Revati A. Khairnar. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.