Drug monitoring by a fully automated high-performance liquid chromatographic technique, involving direct injection of plasma.

A procedure involving direct injection of whole plasma for analyses of drugs by an automated high-performance liquid chromatograph was developed. This system comprised two columns, two pumps, one detector, two programmable switching valves, an automatic sample injector with a cooling device for sample tubes and a microprocessor. Effluents from the first column, containing a drug of interest, were selectively introduced into the second column for further separation. The columns used were an aqueous gel chromatography column (column 1) and an ODS column (column 2). The solvent for column 1 must be weaker than that for column 2, so that the solutes from the former will be enriched at the top of the latter. The validity and applicability of this procedure for the study of drug metabolism were demonstrated with the antibiotic cefmetazole, the anticoagulant warfarin, the antitumour agent carboquone and the anaesthetic ketamine.

Determination of carboquone in plasma and ascites by high performance liquid chromatography after intravenous and intraperitoneal administration in man.

A new method for the determination of carboquone (CQ) in human plasma and ascites by high performance liquid chromatography has been developed. The method is sensitive enough to determine levels as low as 1.0 ng per 1.0 ml of plasma or ascites. The average recovery of CQ from these samples was 89.3 +/- 0.9% (n = 5, mean +/- SD). The method consists of 2 steps, 1) extracting CQ from human body fluids with chloroform and 2) quantization of CQ by chromatography using a mu-Bondapak C18 column, monitored at 340 nm, 2,5-Diethyleneimino-3,6-dimethylbenzoquinone was used as the internal standard. Using this analytical method, the concentration-time profiles of CQ in human body fluids after intravenous and intraperitoneal administrations were obtained. It was recognized that intraperitoneal administration of CQ was advantagenous for the treatment of peritonitis carcinomatosa since an effective concentration could be maintained in ascites for about 6 hr.

Studies on liposome-encapsulated carboquone II. Effect of liposomal encapsulation of carboquone on distribution and clearance in animals.

The effects of encapsulation of carboquone (CQ) in the liposomes were investigated on the plasma clearance and tissue distribution of CQ in rabbit and rat. CQ-Liposome, the liposomes in which CQ was encapsulated, was prepared by the method described in a previous report. By intravenous administration at the same dose. CQ-liposome showed approximately three times higher plasma concentration than free CQ in rabbit and rat. However, prolonged release from liposomes or stabilization of CQ in plasma was not observed by encapsulation. The distribution to lung and reticuloendothelial-rich organs such as liver and spleen was enhanced, but on the contrary the distribution to the peripheral tissues such as muscle and skin was decreased. In rats pretreated with drug free liposomes, high plasma CQ concentration was obtained after intravenous administration of CQ-liposome. From these results, it is considered that the large parts of CQ-liposome is distributed into reticuloendothelial system (RES) and RES is saturable with liposomes. And it is also presumed that the high plasma concentration obtained after intravenous administration of CQ-liposome, would be caused by altering the tissue distribution of CQ by encapsulation.