Doping in sport--2. Quantification of the impurity 19-norandrostenedione in pharmaceutical preparations of norethisterone.
The finding of measurable amounts of 19-norandrostenedione in norethisterone tablets prompted us to develop an assay to quantify this steroid. 19-Norandrostenedione is an anabolic steroid whose use in sport is prohibited by the World Anti-Doping Agency (WADA). The assay was developed using isotope dilution and liquid chromatography-tandem mass spectrometry (LC-MS/MS) for the quantification of 19-norandrostenedione in norethisterone formulations, with [3,4-(13)C(2)]-19-norandrostenedione as the internal standard. The results showed amounts up to 1.01+/-0.01microg (mean+/-S.E.M.) per tablet in those containing 5mg of norethisterone or norethisterone acetate (0.02%, w/w) and up to 0.5+/-0.01microg (mean+/-S.E.M.) per tablet (0.05%, w/w) in oral contraceptive tablets containing 0.35-1.5mg of norethisterone or norethisterone acetate. No tablet tested exceeded the British Pharmacopoeia limit of 0.1% for this impurity.
Walker
Christopher J
CJ
King's College London, Drug Control Centre, Pharmaceutical Science Research Division, Franklin-Wilkins Building, 150 Stamford Street, London SE1 9NH, United Kingdom.
Cowan
David A
DA
James
Vivian H T
VH
Lau
Joanne C Y
JC
Kicman
Andrew T
AT
D000735:Androstenedione / Q000031:analogs & derivatives* / Q000032:analysis / Q000737:chemistry; D002853:Chromatography, Liquid; D004300:Doping in Sports; D015394:Molecular Structure; D009640:Norethindrone / Q000032:analysis* / Q000737:chemistry*; D004364:Pharmaceutical Preparations / Q000032:analysis* / Q000737:chemistry; D015203:Reproducibility of Results; D053719:Tandem Mass Spectrometry
D004364:Pharmaceutical Preparations; D000735:Androstenedione; D009640:Norethindrone; C002828:19-norandrostenedione