Analysis and distribution of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) in biological specimens

We have developed a sensitive (100 ppb), easily performed high performance liquid chromatography (ultraviolet) assay for 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) in biological fluids and tissues. This assay has been used to determine drug levels in plasma and brain of normal dogs receiving BCNU (10 mg/kg) with three infusion protocols: (a) intravenous (5- to 10-minute infusion), (b) intracarotid (30- to 60-minute infusion), and (c) intracarotid (10-minute infusion). The levels of BCNU in the ipsilateral brain were maximized (11.0 and 14.4 micrograms/ml) after the 10-minute intracarotid administration. These levels were 2- to 3-fold greater than those seen using alternative infusions. These direct measurement studies provide strong support for intracarotid BCNU therapy of patients with malignant glioma,