Analysis of blood concentrations and clinical application of risdiplam in patients with spinal muscular atrophy using ultra‐high performance liquid chromatography–tandem mass spectrometry

Abstract Risdiplam, the first oral therapy approved for spinal muscular atrophy and made globally available in 2021, necessitates a highly sensitive and straightforward assay for therapeutic drug monitoring. This is crucial to manage potential toxicities linked to drug concentrations and supervise dosing regimens. A cutting‐edge ultra‐high performance liquid chromatography–tandem mass spectrometry bioassay for risdiplam in human serum has been developed. In this method, analytes were separated on a Phenomenex Kinetex XB C 18 column using a 6.5‐min gradient elution after a single‐step protein precipitation. MS detection was conducted via electrospray ionization in positive mode with selected reaction monitoring. The validated range for risdiplam was determined to be 1.95–125.00 ng/mL. The precision and accuracy of intra‐ and inter‐batch analyses were within ±15%. The novel method met all other established criteria. This assay holds promise for monitoring drug concentrations and guiding clinical decisions in patients with spinal muscular atrophy.