Two-dimensional gas-liquid chromatography electron-capture detection of guanethidine in plasma

Abstract

The treatment of hypertension with guanethidine is now in widespread use (1). Investigations of its biochemical and clinical pharmacology in hypertensive patients have been severely limited due to a lack of adequate analytical methodology for its measurement in plasma. The reported techniques for its estimation in biological fluids include spectrofluorimetric detection (2,3), radioisotopic dilution (4-6), and gas chromatography with electron capture (7) or multiple ion detection (8). The in vi?ro metabolic transformation of guanethidine in rabbit and pig liver homogenates as well as its excretion in rat and human urine have been studied (9,lO). A recent review discusses its metabolism (11). There are large variations in the dose (50-300 pg/kg) necessary for the sufficient control of blood pressure in different individuals as well as many side effects during administration of guanethidine. The cause of this variability has not been extensively investigated since the existing methods for its measurement are too insensitive (7) or are based upon expensive gas chromatographic-mass spectrometric instrumentation (8). We have developed a procedure based on a two-dimensional gas-liquid chromatograph (12,15) utilizing electroncapture detection for the analysis of guanethidine. The method consists of a twostep extraction of plasma followed by hydrolysis, derivatization, and dual gas chromatography. MATERIALS AND METHODS