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A high-performance liquid chromatographic method has been developed for the determination of pipotiazine in human plasma and urine. After selective extraction, pipotiazine and the internal standard (7-methoxypipotiazine) and chromatographed on a column packed with Spherosil XOA 600 (5 micrometers) using a 7:3 (v/v) mixture of diisopropyl either--isooctane (1:1, v/v + 0.2% triethylamine and diisopropyl ether--methanol (1:1, v/v) + 0.2% triethylamine + 2.6% water. The eluted compounds are measured by fluorescence detection. The sensitivity of the method was established at 0.25 ng/ml pipotiazine in plasma and 2 ng/ml pipotiazine in urine (C.V. less than 5%). The method has been successfully applied to a pharmacokinetic study following a single oral administration of 10 mg of pipotiazine.

A high-performance liquid chromatographic method has been developed for the determination of metapramine in human plasma and urine. After selective extraction and derivatization with dansyl chloride, metapramine and the internal standard (maprotiline) are chromatographed on a reversed-phase LiChrosorb RP-18 column using a mixture of water--acetonitrile (35:65) as mobile phase. The eluted compounds are measured using a fluorescence detector. The detection limit of the assay for plasma and urine samples is about 1 ng/ml. The method has been successfully applied in a pharmacokinetic study following intravenous administration of 35 mg of metapramine.

A fully automated high-performance liquid chromatographic method is described for the determination of spiramycin 1 in plasma. First, 1 ml of plasma is diluted with 1.5 ml of 4% acetonitrile containing spiramycin 2 as internal standard, and 1 ml is then injected via an automatic sampling unit. A pneumatic valve, which is remote-controlled by the programmable timer of an integrator, switches the sample, initially injected onto a precolumn for sample clean-up, to an analytical column for sample separation. This method was compared with a microbiological assay and has been successfully applied to pharmacokinetic studies on spiramycin in humans.

A high-performance liquid chromatographic method has been developed for the simultaneous determination of zopiclone and its main metabolites (N-oxide and N-desmethyl derivatives) in biological fluids. After selective extraction (dichloromethane-2-propanol) these compounds are chromatographed on a column packed with Spherisorb ODS-2 (5 micron) using monobasic sodium phosphate-methanol (45:55, v/v). The eluted compounds are measured by fluorescence detection. The limit of detection of the method is 5 ng/ml for zopiclone in plasma and urine and 10 ng/ml for its two main metabolites (coefficient of variation less than 10%). This method has been successfully applied to pharmacokinetic studies of zopiclone and its two main metabolites in healthy subjects and patients with chronic renal failure.