How to improve recovery for QC samples when recovery is low due to matrix effect?

For research use only. Not for use in diagnostic procedures.

Answer

The presence of matrix in quality control samples (QCs) usually causes signal suppression and results in lower recoveries. (In less common cases recovery could be higher than 100% due to signal enhancements).

To resolve this issue, analysts could:

1- Use matrix matched standards: Instead of preparing standards in pure solvents (neat standards), user could spike some clean and analyte free samples with matching matrix at different levels. Extracting these samples would result in matrix matched standards that would have similar matrix effects as Quality controls. This would compensate the loss of signal and low recovery in QC samples.

Spiking matrix matched standards prior to extraction has the advantage of also compensating for any loss of analyte due to extraction.

2- Use of Internal Standards (IS): If an internal standard is added to both standards and QCs, The signal for the IS will also go through a similar matrix effect as that of the Analyte. Use of signal ratio (Analyte to IS) would compensate for matrix effects and result in much better recoveries. Isotopically labeled Internal Standards have the advantage to have almost identical behavior as analyte itself towards matrix. In this case the compensation would be ideal.

Both 1 and 2 above could be used to achieve best recoveries: Using matrix matched standards and spiking them with internal standard as well.