Specific and sensitive determination of medroxyprogesterone acetate in human serum by gas chromatography-mass spectrometry.

The mass fragmentographic determination of medroxyprogesterone acetate (MPA) in serum, using as internal standard medroxyprogesterone propionate (MPP) synthesized from MPA, is described. After addition of MPP, the sera are extracted on Sep-Pak C18 cartridges and MPA and MPP are detected as their respective 3-enol trifluoroacyl esters. Serum samples from 84 patients with breast cancer, daily receiving MPA orally, were determined showing a large variation in MPA concentrations (4-349 ng/ml). Our proposed gas chromatographic-mass spectrometric (GC-MS) method, which can be considered as a reference, was compared with a radioimmunoassay (RIA) method showing a correlation coefficient of 0.73 (n = 69; p much less than 0.001). The assay was also used to determine sequential serum levels of patients receiving a single oral dose of MPA. With only minor adjustments, the GC-MS method allows the determination of serum concentrations of related steroids such as megestrol acetate and cyproterone acetate.