Which statement best defines a valid LC-MS/MS calibration curve?

Which statement best defines a valid LC-MS/MS calibration curve?

• A. Covers the reportable range with good linearity (r^2)
• B. Uses only the highest concentration standards
• C. Requires no back-calculated accuracy
• D. Precision is not a concern for calibration

Answer: (A)

In LC-MS/MS quantification, the calibration curve must span the full reportable range and show a linear response so that instrument signal can be reliably translated into concentrations. A curve with good linearity, typically indicated by an R-squared near 1, ensures that interpolations between calibration points are accurate across the range used for reporting patient results. If you rely only on the highest concentration standards, you risk poor characterization at lower levels and may need to extrapolate, which can introduce errors. Back-calculated accuracy is also essential in calibration validation: you verify that the concentrations predicted by the curve match the known values of the calibrators, confirming the curve truly represents the assay response. Precision matters too because a calibration curve needs to yield consistent results across replicates. Taken together, the statement that a valid LC-MS/MS calibration curve covers the reportable range with good linearity best captures the necessary criteria.