鉄(III)医薬品中の不純物としての鉄(II)測定用紙ベースマイクロ流体デバイスの開発における分析的品質設計

A microfluidic paper-based analytical device (μPAD) was developed for the quantitation of ferrous ions (Fe²⁺) and total iron in iron sucrose administered in iron deficiency anemia. The elemental iron content is 20 mg/mL and USP established a limit of Fe²⁺ as 0.4 % (w/v). The μPAD allowed the quantitation of Fe²⁺ by complexation with 1,10-phenanthroline, forming an orange-red complex analysed by imageJ®. For total iron determination, ferric ion (Fe³⁺) was reduced to Fe²⁺ using ascorbic acid prior to complexation. The device was prepared on chromatographic paper by using the wax printing method. The dimensions of channels and detection zones as well as reagents/sample volumes were optimized using an Analytical Quality by Design (AQbD) approach, focusing on two critical analytical procedure attributes: mean intensity of the colour developed in the detection zones and homogeneity of the colour. By implementing the AQbD, the Method Operable Design Region was defined to account for model uncertainty and experimental variability. The optimized method was linear over 0.10-0.50 mM for Fe²⁺ and 2.0-8.0 mM for total iron, with limits of quantitation of 0.10 and 1.60 mM, respectively. Method performance was evaluated for selectivity, range, sensitivity, trueness, and robustness. Application to commercially available iron sucrose injections showed the accurate quantitation of Fe²⁺ impurities, with results statistically comparable to a validated capillary electrophoresis method. The developed μPAD is a low-cost, portable, and reliable platform for iron determination in pharmaceutical samples, suited to resource-limited settings.