Scholarlink

<p>A robust and environmentally sustainable LC–MS method was developed and optimized using a Box–Behnken Design (BBD) to simultaneously quantify montelukast, etofylline, and theophylline in synthetic plasma and marketed formulations. Design-Expert software (version 13.0) facilitated a systematic exploration of three critical chromatographic variables—methanol concentration, flow rate, and mobile phase pH—across three coded levels, with their effects assessed on retention time (RT) and tailing factor (TF). Response surface methodology and statistical analyses (ANOVA) confirmed model significance and predictive reliability, with second-order polynomial equations describing variable-response relationships. The optimized conditions (78.13% methanol, 1.0&#xa0;mL/min flow rate, pH 4.4) yielded reproducible retention and peak symmetry, with &lt; 5% deviation between predicted and experimental values. Mass spectrometry analysis employed a triple quadrupole instrument in positive ESI mode with SRM transitions: m/z 593.27 (montelukast), m/z 224.22 (etofylline), and m/z 180.164 (theophylline). The validated method met all regulatory criteria per EC guidelines, with excellent linearity (R<sup>2</sup> &gt; 0.999), precision (%CV &lt; 15%), and recovery (99–100.46%). Stability studies demonstrated analyte robustness under various storage conditions. Notably, method greenness was evaluated using Analytical GREEnness (AGREE), ComplexGAPI, Eco-Scale tools and Blue Applicability Grade Index (BAGI), confirming a low environmental footprint due to minimal solvent consumption, non-toxic reagents, and efficient runtime. In addition, the method was successfully applied to quantify analytes in commercial tablet formulation, confirming accuracy, selectivity, and absence of interference. This study not only establishes a highly sensitive, precise, and green LC–MS platform for multi-analyte quantification in biological matrices but also extends its applicability to quality control in marketed products.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Quality by Design-Guided LC–MS Method for Simultaneous Bioanalysis of Montelukast, Theophylline, and Etofylline in Synthetic Plasma

  • 期刊论文

  • 发表日期：

    2025年9月11日

查看全文
  • Gnanasekaran D,
  • Gandhimathi R,
  • Mohana Vamsi Nuli,
  • Pavan Kumar Jaini,
  • Ramanjaneyulu Seemaladinne,
  • Lalitha Repudi,
  • Kumaraswamy Gandla

摘要

A robust and environmentally sustainable LC–MS method was developed and optimized using a Box–Behnken Design (BBD) to simultaneously quantify montelukast, etofylline, and theophylline in synthetic plasma and marketed formulations. Design-Expert software (version 13.0) facilitated a systematic exploration of three critical chromatographic variables—methanol concentration, flow rate, and mobile phase pH—across three coded levels, with their effects assessed on retention time (RT) and tailing factor (TF). Response surface methodology and statistical analyses (ANOVA) confirmed model significance and predictive reliability, with second-order polynomial equations describing variable-response relationships. The optimized conditions (78.13% methanol, 1.0 mL/min flow rate, pH 4.4) yielded reproducible retention and peak symmetry, with < 5% deviation between predicted and experimental values. Mass spectrometry analysis employed a triple quadrupole instrument in positive ESI mode with SRM transitions: m/z 593.27 (montelukast), m/z 224.22 (etofylline), and m/z 180.164 (theophylline). The validated method met all regulatory criteria per EC guidelines, with excellent linearity (R2 > 0.999), precision (%CV < 15%), and recovery (99–100.46%). Stability studies demonstrated analyte robustness under various storage conditions. Notably, method greenness was evaluated using Analytical GREEnness (AGREE), ComplexGAPI, Eco-Scale tools and Blue Applicability Grade Index (BAGI), confirming a low environmental footprint due to minimal solvent consumption, non-toxic reagents, and efficient runtime. In addition, the method was successfully applied to quantify analytes in commercial tablet formulation, confirming accuracy, selectivity, and absence of interference. This study not only establishes a highly sensitive, precise, and green LC–MS platform for multi-analyte quantification in biological matrices but also extends its applicability to quality control in marketed products.