Determination of promethazine in human plasma by automated high-performance liquid chromatography with electrochemical detection and by gas chromatography-mass spectrometry.
A highly specific and sensitive method using automated high-performance liquid chromatography with electrochemical detection (HPLC-ED) and a method using gas chromatography-mass spectrometry (GC-MS) have been developed for the quantitative determination of promethazine in plasma. The lowest detectable concentration by HPLC-ED is 0.1 ng/ml of plasma and by GC-MS 0.5 ng/ml of plasma. The HPLC-ED method incorporates a valve switching unit to prevent all of the electroactive impurities from entering the electrode compartment, thus maintaining the sensitivity of the detector for the analyses of large numbers of samples. The GC-MS method incorporates the highly specific selected-ion monitoring technique. Plasmas derived from healthy subjects each given a single 50-mg oral dose of promethazine were analyzed by both HPLC-ED and GC-MS. The two methods compare favorably with a correlation coefficient of 0.92 and a slope of 1.059. While both methods are suitable for studying single-dose pharmacokinetics of promethazine, the automated HPLC-ED method has a decided advantage in being more sensitive and suitable for unattended overnight analyses of the large number of samples encountered in pharmacokinetic studies. The specificity of the HPLC-ED method is demonstrated by comparison to the GC-MS analysis of biological samples.
D002851:Chromatography, High Pressure Liquid; D004563:Electrochemistry; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D011398:Promethazine / Q000097:blood*
D011398:Promethazine