Modernizing the assay for ammonia in pharmaceuticals

Area of Science:

• Analytical Chemistry
• Pharmaceutical Analysis
• Chromatography

Background:

• Current United States Pharmacopeia (USP) monographs for adenosine and sodium bicarbonate utilize imprecise, outdated color comparison assays for ammonia determination.
• Monograph modernization is essential for ensuring the accuracy and reliability of pharmaceutical quality control testing.

Purpose of the Study:

• To develop and validate modern ion chromatography (IC) assays for quantifying ammonia in adenosine and sodium bicarbonate.
• To replace existing colorimetric methods with more precise and efficient analytical techniques that meet USP requirements.

Main Methods:

• Developed a rapid (<5 min/sample) IC assay using a high-performance cation-exchange column for ammonia in adenosine, detected by suppressed conductivity.
• Developed a distinct IC method employing a high-capacity cation-exchange column to accurately quantify low ammonia concentrations in the presence of high sodium concentrations for sodium bicarbonate.
• Assessed assay performance metrics including precision, accuracy, limits of detection (LOD) and quantitation (LOQ), and robustness according to USP General Chapter <1225>.

Main Results:

• Both IC methods demonstrated excellent precision (retention time RSD <0.1%, peak area RSD <2.3%) and accuracy (average recovery 70-117%).
• The developed methods successfully quantified ammonia in both adenosine and sodium bicarbonate matrices, meeting analytical performance requirements.
• The new IC assays provide reliable and efficient alternatives to the traditional color comparison methods.

Conclusions:

• Ion chromatography offers a superior analytical approach for ammonia determination in pharmaceutical ingredients compared to outdated colorimetric assays.
• The validated IC methods are suitable for modernizing USP monographs for adenosine and sodium bicarbonate, enhancing drug quality and safety.
• These advancements contribute to the ongoing efforts in pharmaceutical analysis for more robust and precise quality control.