Objective  To establish a high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) method for determining the plasma concentration of olverembatinib in leukemia patients, apply it to clinical drug monitoring, and provide reliable basis for rational drug use in clinical practice.

Methods  Ponatinib-d₈ was used as an internal standard, and methanol was used to precipitate plasma proteins and extract olverembatinib. The chromatographic column was Welch Ultimate XB-C18 cloumn (50 mm×4.6 mm, 5 μm), with a column temperature of 60 °C. The mobile phase consisted of an aqueous solution (containing 0.1% formic acid+2 mmol/L ammonium acetate)-methanol solution (containing 0.1% formic acid), with a flow rate of 0.8 mL/min and gradient elution. Electrospray positive ion mode was used, with multiple reaction monitoring scanning. The quantitative ion pair of olverembatinib was  m/ z 533.3→260.1, the qualitative ion pair was m/z 533.3→433.3, and the internal standard ion pair was m/z 541.1→260.2. The plasma samples of 40 leukemia patients taking olverembatinib were monitored and analyzed for concentration, and IBM SPSS Statistics 27.0 and OriginPro 2021 softwares were used for statistical analysis of the results.

Results  The linear range of olverembatinib was 1-250  ng/ mL (r=0.998 0), the lower limit of quantification was 1 ng/mL, the extraction recovery rate was 100.28%~101.27%, the intra-day precision RSD was 1.15%~3.87%, and the inter-day precision RSD was 2.32%~3.68%.

Conclusion  This method is easy to operate, highly specific and sensitive, and can be used to determine the blood concentration of olverembatinib in leukemia patients.

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