Bridging Study: Comparing QQQ and HRMS for Impurity X Quantitation, determining their regulatory alignment, and evaluating method transfer feasibility

In pharmaceutical analysis, selecting the right instrumentation is critical for ensuring precise and regulatory-compliant impurity quantitation. At Emery Pharma, we conducted a bridging study to compare two mass spectrometry techniques—Triple Quadrupole Mass Spectrometry (QQQ) and High-Resolution Mass Spectrometry (HRMS)—for the quantitation of Impurity X in a drug product. This study aimed to assess the performance of both methods, determine their regulatory alignment, and evaluate method transfer feasibility.

Scope of Work

Our study focused on the following objectives:

• Comparative evaluation: Assessing the performance of QQQ and HRMS for detecting and quantifying Impurity X.
• Regulatory alignment: Ensuring that both methods comply with FDA guidelines.
• Method transfer: Determining the feasibility of transitioning the method between QQQ and HRMS.

Key Findings

1. Selectivity and Specificity

To evaluate selectivity, we examined blank samples for potential interferences at the retention time of Impurity X:

• QQQ Approach (Agilent 6470 LC-MS/MS): Blank samples were analyzed and compared to a standard containing Impurity X at its retention time.
• HRMS Approach (Orbitrap Exploris 240): Blank Selected Ion Monitoring (SIM) chromatograms were compared to the standard at the same retention time.
• Results: Both QQQ and HRMS exhibited no interference at Impurity X’s retention time. Additionally, the blank signal was less than 1/10 of the standard signal, confirming high selectivity.

2. Linearity and Range

Linearity was assessed by spiking known amounts of Impurity X into solvent and plotting the instrument response against impurity concentration.

• Both QQQ and HRMS demonstrated strong linearity (R² > 0.9) across the tested range.

3. Accuracy

Accuracy was evaluated by preparing known concentrations of Impurity X at three different levels and comparing the measured values to nominal values.

• Both QQQ and HRMS demonstrated accuracy within 87-110%, ensuring reliable quantitation.

4. In-Matrix Accuracy (Recovery)

To assess recovery, known amounts of Impurity X were spiked into the drug product (DP) and measured.

• Both QQQ and HRMS maintained in-matrix accuracy within 88-108%, demonstrating that matrix effects did not significantly impact quantitation.

Conclusion

Emery Pharma successfully conducted this bridging study to compare QQQ and HRMS for Impurity X quantitation. Our findings highlight:

• Both QQQ and HRMS demonstrated strong linearity (R² > 0.9), accuracy, and in-matrix recovery.
• Both methods provided comparable quantitation of Impurity X, ensuring reliable impurity profiling.
• The study supports method transfer feasibility, offering flexibility for analytical workflows.

This case study and the below video highlights Emery Pharma’s dedication to delivering high-quality, regulatory-compliant analytical solutions for the pharmaceutical industry. Whether you need expert impurity quantitation or seamless method transfer support, our team is here to help. Please see our other videos here or contact us today to see how we can support your analytical needs!