パンoprazoleナトリウム不純物の決定と検証のための安定性指標HPLCおよびUPLC方法の開発と比較

Pantoprazole is a selective proton pump inhibitor used in its sodium form in pharmaceuticals. Determining its impurities is crucial for drug purity and safety.

This study aims to develop a faster impurity analysis method than the European Pharmacopoeia (EP) method.

An Agilent Zorbax SB Phenyl (250 × 4.6 mm, 5.0 µm) column was used for HPLC, and a Restek Ultra Biphenyl (100 × 2.1 mm, 3.0 µm) column for UPLC. A 65:35 (v/v) potassium dihydrogen/dipotassium hydrogen phosphate buffer (pH 7.40)-acetonitrile mixture was the mobile phase. Analyses were performed at 290 nm with flow rates of 1.0 mL/min (HPLC) and 0.25 mL/min (UPLC). Injection volumes were 20 µL (HPLC) and 3.5 µL (UPLC).

The analysis times of the impurity determination methods developed are 15 min shorter for the HPLC method and 30 minutes shorter for the UPLC method compared to the EP method. The developed methods were validated according to ICH guidelines, demonstrating high linearity (R2 > 0.99 over the concentration range of 0.03-2.27 µg/mL), accuracy with mean recoveries ranging from 95.0% to 105.0%, and precision with intra- and inter-day RSD values below 2%. Forced degradation studies under acidic, alkaline, oxidative, thermal, and photolytic conditions confirmed that the methods are stability-indicating, with the ability to separate all major degradation products of pantoprazole sodium.

The method was validated according to International Conference on Harmonisation (ICH) guidelines, and forced degradation studies were also performed. This study presents optimized HPLC and UPLC methods that allow faster impurity analysis and detection of an additional non-compendial impurity, Pantoprazole-N-oxide.

As a result of shorter analysis times, a significant cost reduction has also been proven with numerical data. In addition, a performance-cost comparison of two different analytical technologies was made.