Quantification of homoharringtonine and harringtonine in serum by chemical ionization mass spectrometry.
Homoharringtonine and harringtonine are esters of cephalotaxine and are naturally occurring alkaloids in certain coniferous trees in China. These compounds have been shown to have activity against certain types of leukemia in cell cultures, experimental animals, and initial clinical trials in China, and will undergo Phase I trials in several institutions. A gas chromatographic mass spectrometric technique was developed for the quantification of both drugs in serum. One drug serves as internal standard for the other. The drugs are extracted from serum with dichloromethane and are quantified by monitoring the protonated molecular ions of the trimethylsilyl derivatives obtained by chemical ionization (methane). Masses monitored are: m/z = 690 for homoharringtonine and m/z = 676 for harringtonine. Detection limit: 10 ng ml-1 (20 nmol); reproducibility: 1.6-15.0% in the 0-200 ng ml-1 range. Serum levels of harringtonine reached 145 ng mg-1 upon intraperitoneal injection of 3 mg kg-1 in BDF-3 mice.
D000470:Alkaloids / Q000097:blood*; D000818:Animals; D008401:Gas Chromatography-Mass Spectrometry; D006248:Harringtonines / Q000097:blood*; D000077863:Homoharringtonine; D013058:Mass Spectrometry / Q000379:methods; D051379:Mice
D000470:Alkaloids; D006248:Harringtonines; D000077863:Homoharringtonine