A simplified method for therapeutic drug monitoring of mitotane by gas chromatography-electron ionization-mass spectrometry

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.     

Functional Polymers. XVII. Radical Grafting of Methyl 5-Vinylsalicylate onto Polybutadienes

Abstract

Methyl 5-vinylsalicylate was successfully grafted onto 1, 2-and cis-1,4-polybutadiene. When the grafting reaction was carried out in benzene at 60°C with azobisisobutyronitrile or benzoyl peroxide as the initiator, methyl 5-vinylsalicylate was transformed into grafted poly(methyl 5-vinylsalicylate) with a grafting efficiency of 5–22%. It was very important to carry out the grafting reaction under carefully controlled conditions and at relatively low concentration of polybutadienes, otherwise utilization of methyl 5-vinylsalicylate was low and cross-linking of polybutadiene occurred.