Drug Discov Ther. 2023;17(4):289-293. (DOI: 10.5582/ddt.2023.01043)

Development of a simple high-performance liquid chromatographyultraviolet method for sotorasib quantification in human plasma: Implications for therapeutic drug monitoring

Hikita E, Gando Y, Chubachi H, Shirota M, Kushiyama A, Yasu T


Sotorasib, an oral small-molecule inhibitor, reportedly exerts promising activity against Kirsten rat sarcoma viral oncogene homolog (KRAS)-mutant tumors. However, the currently administered dose may fail to represent the optimal dose based on the therapeutic efficacy. Herein, we developed a simple and sensitive method using high-performance liquid chromatography with ultraviolet (HPLC-UV) to measure the sotorasib concentration in human plasma. The sotorasib calibration curve exhibited linearity across the concentration range of 0.10-20.0 μg/mL (r2 = 0.9999). The coefficients of intraand inter-day validation ranged between 0.79-9.75% and 3.01-6.13%, respectively. The assay accuracy ranged between –3.14 and 5.18%, with > 98.5% recovery. Subsequently, we applied the developed method to estimate sotorasib concentrations in a patient with KRAS G12C-mutated non-small cell lung cancer. We anticipate that our HPLC-UV method will be valuable for assessing the safety and efficacy of sotorasib in larger patient cohorts.

KEYWORDS: HPLC, sotorasib, therapeutic drug monitoring, KRASG12C mutation, non-small cell lung cancer

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