How can we enhance low recovery rates when quality control (QC) samples are influenced by matrix effects?


Date: 10/16/2025
Categories: Academia Omics , ProteinPilot software , Pharma CRO

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Answer

Matrix effects can lead to either signal suppression or enhancement, particularly in quantitative analysis, which can affect the accuracy of results. When a calibration curve is prepared using neat standards (in pure solvent), and quality control samples (QCs) contain matrix components, this can result in variations in signal between the standards and QCs, as well as poor recovery rates.

Usually, the presence of matrix in quality control samples (QCs) can cause signal suppression and result in lower recoveries. Less commonly, recovery from QC samples in matrix could be higher than 100% due to signal enhancement.

To address this issue, analysts can consider the following approaches:

1. Use Matrix-Matched Standards: Instead of preparing standards in pure solvent, analysts can spike clean, analyte-free samples with the corresponding matrix at various levels. By extracting these samples, they create matrix-matched standards that will exhibit similar matrix effects as the quality control samples. This method helps compensate for signal loss and lower recovery rates observed in QC samples. Additionally, spiking matrix-matched standards before extraction helps account for any loss of analyte during the extraction process.

2. Utilize Internal Standards (IS): Adding an internal standard (IS) to both the standards and QCs can be beneficial. The IS signal will undergo similar matrix effects as the analyte signal. By using the signal ratio of the analyte to the internal standard, analysts can compensate for matrix effects, resulting in improved recoveries. Isotopically labeled internal standards are particularly advantageous as they exhibit almost identical behavior to the analyte in relation to the matrix, providing ideal compensation.

Combining both approaches—using matrix-matched standards and spiking them with an internal standard—can lead to the best recovery rates.