Oligonucleotide bioanalysis: sensitivity versus specificity

“Coupling MS/MS with UPLC may improve both assay sensitivity and specificity by providing better chromatographic resolution and sharper peaks ... However, until now,challenges have existed for routinely analyzing oligonucleotides from biological matrices primarily due to the short life of UPLC columns.” The bioanalysis of oligonucleotide therapeutics is constantly evolving, primarily driven by drug development needs and regulatory requirements. The technologies have been comprehensively reviewed by Tremblay and Oldfield. Each method has been used for different study purposes for a period of time. To support preclinical and clinical studies, assay robustness/ruggedness, sensitivity and specificity are critical features for obtaining reliable data...