Abstract
Mitotane is a key drug for the treatment of adrenal cortical carcinoma. Due to its narrow therapeutic window, 14–20 μg/mL, monitoring its concentration is crucially important. In this study, a simplified method for measuring mitotane in plasma using gas chromatography‐electron ionization‐mass spectrometry (GC‐EI‐MS) was developed. Through deproteination and liquid–liquid extraction, mitotane and an internal standard (IS) were extracted from plasma samples. GC‐EI‐MS yielded retention times of 8.2 and 8.7 min, for mitotane and the IS, respectively, with a total run time of 12 min. Selectivity and intra‐/inter‐batch accuracy and precision analyses provided a lower limit of quantification of 0.25 μg/mL, and a calibration curve between 0.25 and 40 μg/mL had good linearity (coefficient of determination = 0.992). The matrix effect factor and percent recovery of the method had good precision. Additionally, long‐term sample stability was observed below 4°C. In a clinical setting, mitotane levels in plasma from an adrenal cortical carcinoma patient were within calibration range. Therefore, this simplified method can be applied to routine therapeutic drug monitoring of mitotane, which may contribute to improved treatment of adrenal cortical carcinoma.
Highlights
Mitotane, a key drug for the treatment of adrenal cortical carcinoma (ACC), has a narrow therapeutic window between 14 and 20 μg/mL; it is desirable to routinely perform therapeutic drug monitoring (TDM)
A measurement method involving a simplified sample preparation procedure has been recently reported by Feliu et al (2017); this method involves the use of an ultra-high performance liquid chromatography (LC) (UPLC) system, which may currently be less common than LC or gas chromatography (GC) systems, UPLC may be more available in future decades
We aimed to develop a widely usable method for the measurement of plasma mitotane levels by GC-EI-MS involving a simplified pretreatment procedure in order to facilitate routine TDM of mitotane
Summary
A key drug for the treatment of adrenal cortical carcinoma (ACC), has a narrow therapeutic window between 14 and 20 μg/mL; it is desirable to routinely perform therapeutic drug monitoring (TDM). A simplified and rapid quantitative method for TDM of mitotane is clinically desired, compared to those of metabolites and chiral bodies. Validated liquid chromatography (LC) methods for the measurement of blood (including plasma and serum) mitotane levels Considering the fast-paced clinical requirements, these conditions are not applicable for routine TDM of mitotane.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
