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<p>Many individuals with diabetes have compromised immune systems and reduced peripheral sensation, making them susceptible to infections. As a result, combination therapy involving antidiabetic drugs and antibiotics has become essential. A newly introduced combination of the antidiabetic drug linagliptin (LIN) and the third-generation cephalosporin antibiotic cefixime (CEF) has been recommended to combat infections in diabetic patients.To optimize therapeutic efficacy and minimize adverse effects associated with this combination therapy, a reliable analytical method was essential for pharmacokinetic analysis and therapeutic drug monitoring. This study present, for the first time, a green high-performance liquid chromatographic method with photodiode array detection (HPLC-PDA) for the simultaneous determination of LIN and CEF in plasma samples. Chromatographic separation was achieved using a Symmetry C<sub>18</sub> column (250&#xa0;mm × 4.6&#xa0;mm, 5&#xa0;μm particle size) under isocratic elution with a mobile phase consisting of 20 mM sodium phosphate (pH 4.3, adjusted with orthophosphoric acid) and methanol (50:50, v/v). The flow rate was set at 0.8 mLmin<sup>− 1</sup>, with a total run time of 12&#xa0;min. The injection volume was 20 µL and the detection was performed at 230&#xa0;nm. The method demonstrated linearity over a range of 50–2000 ng mL<sup>−1</sup>for both LIN and CEF, with limits of detection (LOD) of 24 and 21 ngmL⁻¹ and limits of quantitation (LOQ) of 43 and 45 ngmL⁻¹ for LIN and CEF, respectively. Validation parameters complied with ICH M10 bioanalytical guidelines. Additionally, the method was successfully applied to a pharmacokinetic study comparing drugs efficacy when administered alone versus concurrently. The results demonstrated that co-administration of LIN and CEF significantly altered their bioavailability: LIN C<sub>max</sub> increased by 63.2% and AUC increased by 134.2%, while CEF C<sub>max</sub> decreased by 27.3% and AUC decreased by 23.3%, indicating a bidirectional pharmacokinetic interaction, and underscoring the need for careful monitoring during combination therapy.The greenness of the proposed HPLC-PDA method was evaluated using four metric tools and the findings confirmed the method’s minimal environmental impact. In conclusion, the developed HPLC-PDA method not only provides a reliable tool for therapeutic drug monitoring in clinical practice but also establishes a robust framework for future investigations into drug-drug interactions in human therapeutics.</p>

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Green HPLC-PDA method for simultaneous determination of linagliptin and cefixime with pharmacokinetic application in rats

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月7日

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  • Weam M. Othman,
  • Nehal F. Farid,
  • Nourah Z. Al-zoman,
  • Ibrahim A. Darwish,
  • Samah S. Saad,
  • Fatma F. Abdallah

摘要

Many individuals with diabetes have compromised immune systems and reduced peripheral sensation, making them susceptible to infections. As a result, combination therapy involving antidiabetic drugs and antibiotics has become essential. A newly introduced combination of the antidiabetic drug linagliptin (LIN) and the third-generation cephalosporin antibiotic cefixime (CEF) has been recommended to combat infections in diabetic patients.To optimize therapeutic efficacy and minimize adverse effects associated with this combination therapy, a reliable analytical method was essential for pharmacokinetic analysis and therapeutic drug monitoring. This study present, for the first time, a green high-performance liquid chromatographic method with photodiode array detection (HPLC-PDA) for the simultaneous determination of LIN and CEF in plasma samples. Chromatographic separation was achieved using a Symmetry C18 column (250 mm × 4.6 mm, 5 μm particle size) under isocratic elution with a mobile phase consisting of 20 mM sodium phosphate (pH 4.3, adjusted with orthophosphoric acid) and methanol (50:50, v/v). The flow rate was set at 0.8 mLmin− 1, with a total run time of 12 min. The injection volume was 20 µL and the detection was performed at 230 nm. The method demonstrated linearity over a range of 50–2000 ng mL−1for both LIN and CEF, with limits of detection (LOD) of 24 and 21 ngmL⁻¹ and limits of quantitation (LOQ) of 43 and 45 ngmL⁻¹ for LIN and CEF, respectively. Validation parameters complied with ICH M10 bioanalytical guidelines. Additionally, the method was successfully applied to a pharmacokinetic study comparing drugs efficacy when administered alone versus concurrently. The results demonstrated that co-administration of LIN and CEF significantly altered their bioavailability: LIN Cmax increased by 63.2% and AUC increased by 134.2%, while CEF Cmax decreased by 27.3% and AUC decreased by 23.3%, indicating a bidirectional pharmacokinetic interaction, and underscoring the need for careful monitoring during combination therapy.The greenness of the proposed HPLC-PDA method was evaluated using four metric tools and the findings confirmed the method’s minimal environmental impact. In conclusion, the developed HPLC-PDA method not only provides a reliable tool for therapeutic drug monitoring in clinical practice but also establishes a robust framework for future investigations into drug-drug interactions in human therapeutics.