Quantitative analysis of norethindrone in milk using deuterated carrier and gas chromatography-mass spectrometry.

A specific assay has been developed to quantitate norethindrone (17α-ethinyl-17β-hydroxy-estr-4-ene-3-one) in human milk by multiple ion detection technique using gas chromatography-mass spectrometry. 14,15-D2-norethindrone was synthesized and used as an internal standard and carrier. After addition of internal standard, the milk samples were extracted using Amberlite XAD-2 columns and further purified on Sephadex LH-20 columns. O-methoxime-trimethylsilyl ether derivatives of the purified samples were used for analysis. The analysis of known amounts of norethindrone added to control milk samples showed high precision and reproducibility. The assay method was used to measure levels of norethindrone in milk samples of five women inserted with single silastic implant D containing 40 mg nore-thindrone acetate. The mean level at three weeks post insertion was 208 pg/ml which then showed a slow and steady decline.