Therapeutic drug monitoring of mitotane: Analytical assay and patient follow-up.
Biomed Chromatogr
; 31(11)2017 Nov.
Article
in En
| MEDLINE
| ID: mdl-28432798
ABSTRACT
Adrenocortical carcinoma (ACC) is an aggressive malignancy of the adrenal gland. Mitotane (o,p'-DDD) is the most effective chemotherapy for ACC. According to the literature, mitotane plasma trough concentrations within 14-20 mg L-1 are correlated with a higher response rate with acceptable toxicity. Therapeutic drug monitoring (TDM) of mitotane is therefore recommended. The aim of this study was to propose a robust and simple method for mitotane quantification in plasma. The validation procedures were based on international guidelines. Sample preparation consisted of a single protein precipitation with methanol using 100 µL of plasma. The supernatant was submitted to liquid chromatography coupled with ultra-violet detection at 230 nm. Mitotane retention time was 7.1 min. The limit of detection was 0.1 mg L-1 and the limit of quantification was 0.78 mg L-1 . The assay demonstrated a linear range of 0.78-25 mg L-1 with correlation coefficients (r2 ) at 0.999. Inter- and intra-assay precision was <4.85%. Evaluation of accuracy showed a deviation <13.69% from target concentration at each quality control level. This method proved easy and rapid to perform mitotane TDM and required a small volume of sample. It was successfully applied to routine TDM in our laboratory.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Chromatography, High Pressure Liquid
/
Drug Monitoring
/
Mitotane
Type of study:
Guideline
/
Prognostic_studies
Limits:
Adult
/
Female
/
Humans
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Male
/
Middle aged
Language:
En
Journal:
Biomed Chromatogr
Year:
2017
Document type:
Article
Affiliation country:
France