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Accurate quantification of biomarkers has always been a challenge for many bioanalytical scientists due to their endogenous nature and low concentration in biological matrices. Different analytical approaches have been developed for quantifying biomarkers including enzyme-linked immunosorbent assay, immunohistochemistry, western blotting, and chromatographic techniques assisted with mass spectrometry. Liquid chromatography–tandem mass spectrometry-based quantification of biomarkers has gained more attention over other traditional techniques due to its higher sensitivity and selectivity. However, the primary challenge lies with this technique includes the unavailability of a blank matrix for method development. To overcome this challenge, different analytical approaches are being developed including surrogate analyte and surrogate matrix approach. Such approaches include quantification of biomarkers in a surrogate matrix or quantification of an isotopically labeled surrogate analyte in an authentic matrix. To demonstrate the authenticity of the surrogate approach, it is mandatory to establish quantitative parallelism through validation employing respective surrogate analytes and surrogate matrices. In this review, different bioanalytical approaches for biomarker quantification and recent advancements in the field aiming for improvement in the specificity of the techniques have been discussed. Liquid chromatography–tandem mass spectrometry-based surrogate approaches for biomarker quantification and significance of parallelism establishment in both surrogate matrix and surrogate analyte-based approaches have been critically discussed. In addition, different methods for demonstrating parallelism in the surrogate method have been explained.

Advancement in Analytical Strategies for Quantification of Biomarkers with a Special Emphasis on Surrogate Approaches