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article · Scientific Reports

Green spectrophotometric methods for the determination of metformin–curcumin combination: ICH validation and preliminary bioanalytical applications

2026Open accessFayoum University

In plain language

Combining metformin and curcumin offers therapeutic benefits for diabetes management, pairing glucose reduction with antioxidant and anti-inflammatory effects. To support this combination therapy, three complementary and environmentally sustainable spectrophotometric methods were developed and validated for analyzing dosage forms and human plasma. A zero-order method selectively measures curcumin, a first-derivative technique simultaneously quantifies both substances, and a ratio subtraction approach determines metformin without requiring prior physical separation. All procedures displayed strong linearity between 0.5 and 20.0 micrograms per millilitre alongside high sensitivity, satisfying International Council for Harmonisation validation criteria. Tested on raw materials, spiked pharmaceutical formulations, and spiked human plasma, the methods achieved recovery rates ranging from 98.73% to 101.06% with high precision. Greenness assessments confirmed their environmental compatibility for sustainable analytical operations.

Key takeaways

  • Three complementary spectrophotometric methods were developed to determine metformin and curcumin without prior physical separation.
  • The methods demonstrated high linearity from 0.5 to 20.0 micrograms per millilitre and met International Council for Harmonisation validation standards.
  • Testing on raw materials, spiked pharmaceutical formulations, and spiked human plasma yielded recoveries between 98.73% and 101.06%.
  • Greenness evaluations verified the environmental sustainability of the proposed procedures for routine testing.

Why it matters

Co-administering metformin and curcumin holds therapeutic potential in diabetes treatment, but monitoring the combination often requires complex procedures. Providing simple, environmentally sound spectrophotometric techniques enables laboratories to assess both compounds accurately in drugs and biological samples. This offers an accessible, cost-effective alternative to resource-intensive testing while reducing hazardous chemical waste in pharmaceutical analysis.

Commercialisation angle

These methods are relevant to pharmaceutical quality control teams and bioanalytical research laboratories monitoring metformin and curcumin formulations. Because they avoid physical separation stages and reduce hazardous solvent use, they can lower operational costs and improve sustainability. Having been validated on raw materials, pharmaceutical dosage forms, and spiked plasma, the methods represent applied, tested tools ready for implementation in routine laboratory workflows.

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Abstract

Abstract The combined therapeutic use of Metformin and Curcumin has attracted growing interest in diabetes management, owing to metformin’s glucose-lowering effect and curcumin’s antioxidant and anti-inflammatory activities. This clinical relevance necessitates reliable analytical methods for their simultaneous determination. In this study, three simple, selective, and cost-effective complementary spectrophotometric methods were developed and validated for the analysis of metformin and curcumin in dosage forms and human plasma. A zero-order spectrophotometric method enabled the selective determination of curcumin, while a first-derivative method allowed simultaneous quantification of both analytes with improved spectral resolution. A ratio subtraction method was also established for selective metformin determination in the presence of curcumin, effectively resolving spectral overlap without prior separation. All methods exhibited excellent linearity over the concentration range of 0.5–20.0 µg mL − 1 ( r ≥ 0.999). The methods also demonstrated high analytical sensitivity, with limits of detection and quantitation ranging from 0.08 to 0.15 µg mL − 1 and 0.23 to 0.45 µg mL − 1 , respectively. Validation following ICH guidelines confirmed satisfactory accuracy, precision, and selectivity. Statistical comparison with reference methods using Student’s t-test and F-test showed no significant differences at the 95% confidence level. The proposed methods were successfully applied to the determination of both drugs in raw materials, metformin pharmaceutical formulations spiked with curcumin, and spiked human plasma, demonstrating excellent accuracy and precision, with recoveries ranging from 98.73% to 101.06% and RSD values not exceeding 1.50%. Greenness assessment demonstrated environmental compatibility, supporting their use as sustainable analytical tools for routine quality control and bioanalytical applications.

Research topics

  • Analytical Methods in Pharmaceuticals
  • Curcumin's Biomedical Applications
  • Electrochemical sensors and biosensors

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DOI: 10.1038/s41598-026-67101-z

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