[Readers Insight] Matrix Effects in Mass Spectrometry: Why They Matter

For analysts working on mass spectrometry, it is often notable that some national standard methods require calibration curves prepared in pure solvent, while others require them prepared in blank matrix.

The difference between methods reflects whether matrix effects introduced during sample preparation and ionization must be corrected. If matrix effects are significant, then the calibration curves must be prepared in blank matrix; otherwise, preparing in pure solvent is sufficient.

It is easy to notice that, in many standard methods, only the recovery data is provided, yet matrix effect data is omitted — but is recovery rate the only measure in judging method accuracy?

To clarify the relationship between recovery and matrix effects, their fundamentals and calculation formulas must be grasped first.

During sample preparation, analytes loss can occur due to inefficient extraction, heating, oxidation, pH, adsorption/desorption, among many other reasons, and recovery is calculated by the theoretical spike amount minus the losses.

Matrix effect, on the other hand, occur in the ion source when co-extracted matrix components alter the analyte’s ionization efficiency through competition or facilitation, thereby changing the measured response.

When matrix effects are not assessed or corrected, the apparent recovery reported from an experiment is the combined result of preparation losses and ionization alteration.

For example, if 100 units of analyte are spiked and 20 units are lost during preparation, the true recovery is 80. If the matrix causes 50% ion suppression, the measured signal becomes 80 × 50% = 40, and the apparent recovery is 40.

Conversely, if 100 units are spiked, 50 units are lost (true recovery 50), but the matrix enhances ionization by doubling the response (this is known as positive effect, where the matrix acts as a facilitator rather than a competitor), the measured signal becomes 50 × 200% = 100, producing an apparent recovery of 100.

In the latter case, a 100% apparent recovery conceals substantial preparative loss offset by matrix enhancement; such a result is unreliable and may vary widely with different sample types.

ME < 85% indicates suppression; 85% ≤ ME ≤ 115% indicates negligible matrix effect; ME > 115% indicates enhancement.

The results revealed that in water matrix, the DMCs have ME’s between 100% and 113%, which are negligible, therefore solvent calibration was applied; whereas in milk and cream matrices, the ME’s reached 150% to 169% and 160% to 275%, both showing enhancement, thereby matrix calibration was applied.