Comparison of three parallelism assessment methods of biomarker quantification by LC-MS/MS: a case study of the bioanalysis of creatinine in human urine samples.

Background: Currently, no regulatory guidelines are available for parallelism assessment for LC-MS biomarker quantification. Spike recovery, standard addition and dilutional linearity are recommended with no mention of the implications of applying these approaches. Results: Here, using human urine creatinine, the authors compared spike recovery and standard addition in LC-MS biomarker quantification, and evaluated a new hybrid approach: parallelism QCs. The authors drew different conclusions based on which approach was used (<15% cutoff). Conclusion: Current recommended approaches may lead to different conclusions and are not equivalent and interchangeable. The authors recommend that standard addition should be the universal 'go-to' method for LC-MS biomarker parallelism assessment; parallelism QCs, which consider the total concentration as the theoretical value, can be used if the authentic matrix is limited.