Doping in sport-2. Quantification of the impurity 19-norandrostenedione in pharmaceutical preparations of norethisterone

Article abstract of DOI:10.1016/j.steroids.2008.10.006

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 [3,4-¹³C₂]-19-norandrostenedione as the internal standard. The results showed amounts up to 1.01 ± 0.01 μg (mean ± S.E.M.) per tablet in those containing 5 mg of norethisterone or norethisterone acetate (0.02%, w/w) and up to 0.5 ± 0.01 μg (mean ± S.E.M.) per tablet (0.05%, w/w) in oral contraceptive tablets containing 0.35-1.5 mg of norethisterone or norethisterone acetate. No tablet tested exceeded the British Pharmacopoeia limit of 0.1% for this impurity.

Full text of DOI:10.1016/j.steroids.2008.10.006

steroids 7 4 ( 2 0 0 9 ) 335–340
available at www.sciencedirect.com
journal homepage: www.elsevier.com/locate/steroids
Doping in sport—2. Quantification of the impurity
1
9-norandrostenedione in pharmaceutical
preparations of norethisterone
Christopher J. Walker, David A. Cowan, Vivian H.T. James,
∗
Joanne C.Y. Lau, Andrew T. Kicman
King’s College London, Drug Control Centre, Pharmaceutical Science Research Division, Franklin-Wilkins Building,
1
50 Stamford Street, London SE1 9NH, United Kingdom
a r t i c l e i n f o
a b s t r a c t
Article history:
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 [3,4-13C2]-19-norandrostenedione as the internal standard. The results
showed amounts up to 1.01 ± 0.01 ␮g (mean ± S.E.M.) per tablet in those containing 5 mg of
norethisterone or norethisterone acetate (0.02%, w/w) and up to 0.5 ± 0.01 ␮g (mean ± S.E.M.)
per tablet (0.05%, w/w) in oral contraceptive tablets containing 0.35–1.5 mg of norethisterone
or norethisterone acetate. No tablet tested exceeded the British Pharmacopoeia limit of 0.1%
for this impurity.
Published on line 1 November 2008
Keywords:
Norethisterone
19-Norandrostenedione
Impurity
Doping
©
2008 Elsevier Inc. All rights reserved.
1
.
Introduction
not been considered previously. At the time of our start-
ing this work in 2005, the British Pharmacopoeia [4] did
not list any named impurities in norethisterone powder but
preliminary work in our laboratory using alumina column
chromatography and GC–MS showed measurable amounts
of 19-norandrostenedione but not nandrolone in two brands
of norethisterone tablets. Subsequently the 2007 [5] and the
2008 [6] editions of the British Pharmacopoeia listed steroidal
impurities, including 19-norandrostenedione. For norethis-
terone, HPLC with ultra violet detection is the recommended
pharmacopoeial method for the analysis of its ‘related sub-
stances’. From a forensic perspective, mass spectrometry is
preferred for detection because of its specificity and therefore
we developed an LC–MS/MS method to identify and quantify
the impurity 19-norandrostenedione in norethisterone con-
The typical synthetic route by which norethisterone is
produced (Fig. 1) [1] employs 19-norandrostenedione and
nandrolone as intermediates, both of which are anabolic
steroids whose use in sport is prohibited by WADA. The
chemical synthesis is efficient but a minor amount of 19-
norandrostenedione remains unconverted, as its presence
has been reported in the mother liquor product, as mea-
sured by high-pressure liquid chromatography (HPLC) and
gas chromatography, respectively [2,3]. It occurred to us
that 19-norandrostenedione could be a residue present in
pharmaceutical preparations of norethisterone, which could
be a potential source of urinary 19-norandrosterone from
endogenous metabolism of these trace amounts. This has
∗
Corresponding author.
E-mail address: andrew.kicman@kcl.ac.uk (A.T. Kicman).
0039-128X/$ – see front matter © 2008 Elsevier Inc. All rights reserved.
doi:10.1016/j.steroids.2008.10.006

3
36
steroids 7 4 ( 2 0 0 9 ) 335–340
Fig. 1 – Summary of norethisterone synthesis [1]. Birch reduction (lithium in liquid ammonia) of estradiol methyl ether (I)
and then mild acid hydrolysis results in 19-nortestosterone (III). Oxidation of 19-nortestosterone results in
1
9-norandrostenedione (IV) and treatment with ethyl orthoformate results in (V). Then acetylene in the presence of
potassium t-amylate forms (VI), which is hydrolyzed to form norethisterone (VII).
taining products. In the present study, 32 products available on
the world market were analyzed using this assay for possible
use in subsequent studies.
218790; Sandoz), (5 mg; 627842; Alpharma), and (5 mg; 764439;
CP Pharmaceuticals) were purchased from AAH Hospital
services (Coventry). Norinyl-1 (1 mg; 134560; Pharmacia),
Norimin (1 mg; 223570; Pharmacia), Brevinor (1 mg; 242930;
Pharmacia), Trinovum (1 mg peach; 6LSK000; Janssen-Cilag
Ltd.; UK), Ovysmen (0.5 mg; 7BS1F00; Janssen-Cilag Ltd.; UK),
Binovum (1 mg peach; 6LSK000; Janssen-Cilag Ltd.), Loestrin 30
(1.5 mg; 519991; Galen), and Loestrin 20 (1 mg; 519550; Galen)
were purchased from Kalmak Chemist Ltd. (London, UK).
Sunolut (5 mg; lot number not available; Sunward Pharma-
ceuticals; Malaysia), Norcolut (5 mg; T43253B; Gedeon Richter;
2
.
Experimental
2
.1.
Materials and methods
Glacial acetic acid (17.47 M), chloroform, ethyl acetate, and
hexane, all analytical reagent grade, acetonitrile, cyclohex-
ane, and methanol, all HPLC grade, were purchased from
Fisher Scientific (Loughborough, UK). Alumina TLC plates
Malaysia), Primolut
N (5 mg; 33044; Schering; Malaysia),
Noriday (0.35 mg; 96600; Pharmacia; Malaysia), and generic
norethisterone tablets (5 mg; lot number not available; UPHA;
Malaysia), were donated by Dr. Aishah Latiff. Primolut N
(5 mg; WEB28G; Schering; Australia), Noriday (0.35 mg; 581230;
Pharmacia; Australia), Locilan (0.35 mg; 165310; Pharmacia;
Australia), and Micronor (0.35 mg; 05AS093; Janssen-Cilag
Ltd.; Australia) were donated by Dr. Ray Kaslauskas. Primolut
Nor (5 mg; WEB2G8; Schering; Sweden) and Mini PE (0.35 mg
210880; Pfizer; Sweden) were donated by Dr. Mats Garle, and
Primolut Nor (5 mg; 12023B; Schering; Italy) and Primolut Nor
(5 mg; WEB2G7; Schering; Greece) were donated by Prof. Chris
Marriott.
(
Macherey Nagel 20 cm × 20 cm ALOX N 254 nm) and formic
acid (Aristar, BDH) were purchased from VWR International
Lutterworth, UK). Chromium trioxide (99.9%), ethisterone,
(
and diethyl ether (spectrophotometric grade) were purchased
from Sigma–Aldrich (Poole, UK). Purified water was obtained
from an ELGA Purelab Maxima (Vivendi Water Systems High
Wycombe, UK). Alumina (neutral, particle size 0.05–0.15 mm)
was purchased from Fluka (Poole, UK). The reference steroid
[
3,4-13C2]-19-nortestosterone was purchased from LGC Pro-
mochem (Teddington, UK). Norethisterone was purchased
from Steraloids (Newport, RI, USA). A Chromato-vue cabinet
and Mineralight Lamp (multi-wavelength 366/254 nm) Ultra
Violet Products Inc. (San Gabriel, CA, US) were used to view
the TLC plates.
2
.3.
Synthesis and purification of
13
[3,4- C2]-19-norandrostenedione internal standard
2
.2.
Tablet preparations
This was based on the method described by Wilds and Nel-
son [7]. Chromium (VI) oxide (1.8 mg, 18 ␮M) was dissolved in
0.5 mL acetic acid (95%, v/v) and slowly added to [3,4-13C2]-
19-nortestosterone (6.6 mg, 23.9 ␮M) dissolved in glacial acetic
acid (1 mL) and allowed to react for 2 h at room temperature.
The reaction mixture was neutralized with sodium hydroxide
(10 M) over ice. The solution was transferred to a separating
funnel and extracted with distilled diethyl ether (20 mL). The
Micronor (norethisterone dose 0.35 mg; Batch/Lot 05FS064;
Manufacturer Janssen-Cilag Ltd.), Micronor HRT (1 mg;
0
4HS40S; Janssen-Cilag Ltd.), Utovlan (5 mg; batches 194470
and 154820; Pharmacia), Noriday (0.35 mg; 196890; Pharma-
cia), Primolut N (5 mg; batches 24088A and WEA0XT; Schering)
and generic norethisterone tablets (5 mg; batches 191610 and

steroids 7 4 ( 2 0 0 9 ) 335–340
337
Fig. 2 – GC–MS analysis of the synthesized internal standard after TLC purification, following TMS derivatization. (a) An
13
extracted ion chromatogram of m/z 418 showing a peak at 23.56 min for C2-norandrostenedione; (b) the extracted ion
chromatogram of m/z 420 showing a peak at 23.56 min due to the contribution of natural stable isotopes, such as Si, 30Si
29
1
3
13
and C in C2-norandrostenedione and (c) a full scan mass spectrum of the peak at 23.56 min. The arrow marks the
expected retention time for nandrolone (23.9 min).
mixture was shaken, allowed to settle and the ether layer
was collected. This was repeated six more times. Anhydrous
sodium sulfate was added to the combined ether fraction and
allowed to stand for 10 min. Full scan GC–MS analysis of a
2.4.
standards
Preparation of extracted 19-norandrostenedione
For the quantification of 19-norandrostenedione in the tablets,
standards of the following concentrations 10, 30, 50, 100, 150,
300, 450, and 1000 ng/mL were prepared in triplicate in 2 mL
volumes of purified water. The standards were extracted in the
same manner as the tablets except the extracts were dissolved
in 0.8 mL of methanol:water (87.5:12.5) containing 0.1% formic
acid (v/v). The final solvent composition was the same but the
standards do not contain any norethisterone.
portion of the ether extract showed that significant amounts
of unreacted [3,4-13C2]-19-nortestosterone remained as well
as the desired product, [3,4-13C2]-19-norandrostenedione. The
◦
ether was evaporated to dryness under nitrogen at 35 C. The
residue was dissolved in 3 mL of chloroform:cyclohexane:ethyl
acetate (60:24:16, v/v/v) and a portion was submitted to
thin-layer chromatography using alumina TLC plates and
a
(
mobile phase of chloroform:cyclohexane:ethyl acetate
60:24:16, v/v/v). The plate was viewed under UV light at
54 nm the R values for [3,4-13C2]-19-norandrostenedione and
2
.5.
Preparation of unextracted 19-norandrostenedione
standards (to assess extraction recovery)
2
[
f
3,4-13C2]-19-nortestosterone were 0.60 and 0.24, respectively.
Standards of the following concentrations 10, 30, 50, 100, 150,
The alumina containing the [3,4-13C2]-19-norandrostenedione
was removed from the plate and washed with methanol to
remove the steroid. A small portion of this material was
derivatized to form the bis-trimethylsilyl (TMS) derivatives
and analyzed by GC–MS. The retention time of the synthesized
300, 450, and 1000 ng/mL were prepared in triplicate in 0.7 mL
of methanol:water (87.5:12.5) containing 0.1% formic acid
(
(
v/v). To each vial 0.1 mL [3, 4-13C2]-19-norandrostenedione
1 ␮g/mL) was added and the vial was capped securely.
[
3,4-13C2]-19-norandrostenedione matches closely that of 19-
norandrostenedione, and the full scan spectrum of [3,4-13C2]-
9-norandrostenedione gives m/z 418, 403, and 196 (Fig. 2) with
2
.6.
Extraction procedure
1
Three tablets of each type were weighed and placed in 20 mL
round-bottomed tubes. To each tube 2 mL of water were added,
the tubes were vortex mixed for 30 s and sonicated for 45 min.
To each tube 100 ng of [3,4-13C2]-19-norandrostenedione
very similar relative abundances to the equivalent m/z val-
ues 416, 401, and 194 in authentic 19-norandrostenedione, but
with a two atomic mass unit shift because of the two 13C. No
other steroid was found to be present.
(
0.1 mL of 1 ␮g/mL) and 5 mL of chloroform were added, vortex

3
38
steroids 7 4 ( 2 0 0 9 ) 335–340
2
.7.
LC–MS/MS conditions
Chromatographic separation was performed on an Agilent
1
100 HPLC system using a Zorbax Stable Bond-C18 column
◦
(
50 mm × 2.1 mm, 5 ␮m particle size) heated to 40 C. The
mobile phase was a methanol:water (53:47, v/v) mix con-
taining 0.1% formic acid (v/v), delivered at a flow rate of
0
3
.2 mL/min. This was coupled to an Applied Biosystems API
200 triple quadrupole mass spectrometer with a Turbo Ion-
spray source operating in the positive ion mode. The optimized
source conditions were source heater probe temperature
◦
5
1
4
50 C, Turbo Ionspray voltage 5500 V, curtain gas setting of
0 psi, collision gas setting of 3, ion source gas 1 setting of
5 psi, ion source gas 2 setting of 50 psi, declustering potential
of 41 V, entrance potential of 4.5 V, cell exit potential of 10 V,
and collision energy of 33 V. Selected reaction monitoring
(
SRM) was carried out on specific product ions after collision-
Fig. 3 – Calibration line for 19-norandrostenedione using
LC–MS/MS, including magnification of the graph for the
lower concentrations (inset) (equation y = 0.0094x + 0.0195,
correlation coefficient = 0.9999).
induced dissociation of the protonated molecules. These
were m/z 273 (protonated molecule, [M+H] ) to 109 (dwell time
4
(
+
00 ms), 197, and 83 for 19-norandrostenedione and m/z 275
[M+H] ) to 111 (dwell time 400 ms), 197, and 85 for [3,4-13C2]-
+
19-norandrostenedione. The dwell time for each transition
mixed for 30 s, rotary mixed for 10 min, and centrifuged at
was 200 ms unless otherwise stated. The injection volume
was 10 ␮L. The retention times for 19-norandrostenedione
and [3,4-13C2]-19-norandrostenedione were 4.67 and 4.70 min,
respectively. The flow was diverted to waste at 6 min to
prevent the large amount of norethisterone contaminating
1
320 × g for 5 min. The aqueous (upper) layer was transferred
to a tube containing another 5 mL of chloroform and the mix-
ing and centrifugation steps were repeated. The aqueous layer
was removed and discarded. The chloroform extracts were
◦
+
combined and evaporated to dryness under nitrogen at 55 C.
the system. Norethisterone m/z 299 ([M+H] ) to 109 and
+
To the residue 0.7 mL of methanol was added, vortex mixed
until it had dissolved, 0.1 mL of water containing 0.8% formic
acid (v/v) was added, and vortex mixed briefly. The extracts
were transferred to 1.5 mL tubes, centrifuged at 10,000 × g for
nandrolone m/z 275 ([M+H] ) to 109 were also monitored.
3.
Results
5
min and a portion was transferred to an autosampler vial,
which was then capped securely. The extracts were analyzed
by LC–MS/MS.
The concentration of 19-norandrostenedione in each tablet
was interpolated from the calibration line constructed using
Fig. 4 – The mean amount of 19-norandrostenedione per tablet. The tablets in the top panel are 5 mg doses and those in the
lower panel are mostly oral contraceptive preparations, and one hormone replacement therapy (HRT) containing
0
.35–1.5 mg.

steroids 7 4 ( 2 0 0 9 ) 335–340
339
Table 1 – Amount of 19-norandrostenedione in 5 mg
norethisterone tablets to treat gynecological problems.
Table 2 – Amount of 19-norandrostenedione in oral
contraceptive tablets containing 0.35–1.5 mg of
norethisterone.
Tablet
Mean amount of
Relative amount of
norandrostenedione norandrostenedione
Tablet
Mean amount of
Relative amount of
(ng)
(%)
norandrostenedione norandrostenedione
(
ng)
(%)
Sandoz
Sunolut
Sandoz
Utovlan
CP Pharma
Norcolut
UPHA
1015 ± 6
632 ± 4
579 ± 6
499 ± 5
482 ± 17
246 ± 4
215 ± 1
200 ± 3
187 ± 2
175 ± 1
146 ± 1
103 ± 3
57 ± 4
0.0203
0.0126
0.0116
0.0100
0.0096
0.0049
0.0043
0.0040
0.0037
0.0035
0.0029
0.0021
0.0011
0.0009
0.0006
0.0006
Norinyl-1
Norimin
Brevinor
Noriday
Noriday
499 ± 6
299 ± 9
265 ± 11
159 ± 2
158 ± 1
113 ± 1
94 ± 2
0.0499
0.0299
0.0531
0.0455
0.0451
0.0324
0.0094
0.0080
0.0154
0.0107
0.0032
0.0118
0.0036
0.0103
0.0087
0.0017
Mini PE
Utovlan
Micronor HRT
Trinovum (peach)
Locilan
Ovysmen
Loestrin 30
Noriday
Loestrin 20
Micronor
Micronor
Primolut Nor
Primolut Nor
Primolut Nor
Alpharma
Primolut N
Primolut N
Primolut N
Primolut N
80 ± 53
54 ± 1
53 ± 13
48 ± 2
41 ± 1
44 ± 1
36 ± 1
29 ± 1
36 ± 0.2
30 ± 1
28 ± 2.3
Binovum (peach)
17 ± 0.4
a ratio of the peak area of 19-norandrostenedione (m/z
09) to that of [3,4-13C2]-19-norandrostenedione (m/z 111).
Linear regression lines were calculated and the correla-
tion coefficients were better than 0.995 in all cases (e.g.
Fig. 3). All the tablets analyzed contained measurable quan-
tities of 19-norandrostenedione (Fig. 4). The amount of
tablet containing 5 mg of norethisterone. The extracted ion
chromatograms, of 19-norandrostenedione and [3,4-13C2]-
19-norandrostenedione, for one of these tablets are shown
1
alongside those for
a standard containing 1 ␮g of 19-
norandrostenedione (Fig. 5). The highest proportion found was
0.05% (w/w) so none exceeded the limit set by the British Phar-
macopoeia (0.1%). The recovery of 19-norandrostenedione
was determined from the peak area ratios of the extracted
standards versus the unextracted standards and the mean
1
9-norandrostenedione found per tablet and the proportion
relative to norethisterone are detailed in Tables 1 and 2.
The highest absolute amount was 1.01 ␮g, this was in a
Fig. 5 – LC–MS/MS extracted ion chromatograms for m/z 109 for 19-norandrostenedione (a and c) and m/z 111 for the
internal standard, [3,4-13C2]-19-norandrostenedione (b and d) from the tablet containing ∼1.01 ␮g 19-norandrostenedione (a
and b) and a standard containing 1 ␮g 19-norandrostenedione (c and d).

3
40
steroids 7 4 ( 2 0 0 9 ) 335–340
recovery (n = 3) ranged from 95.1 to 100.2% across the concen-
trations tested.
contribution of norethisterone compared with the impurity
19-norandrostenedione to urinary 19-norandrosterone and
the results of this study are published in this issue [9].
4
.
Discussion
Acknowledgement
The LC–MS/MS method was developed to reliably mea-
sure small amounts 19-norandrostenedione, the much larger
amount of norethisterone being diverted to waste to
avoid overloading the detector and potential contamination.
Our preliminary finding of measurable amounts of 19-
norandrostenedione in two brands of norethisterone tablets
was a concern to us as a trace of this residue, that is
present in pharmaceutical preparations of norethisterone,
would be a potential source of urinary 19-norandrosterone
as a consequence of endogenous conversion. This had not
been considered previously. WADA accredited laboratories are
required to report an ‘Adverse Analytical Finding’, for any
urine sample containing 19-NA in a concentration greater
than 2 ng/mL with a specific gravity equal to or lower than
The authors are grateful to the United States Anti-Doping
Agency (USADA) for their financial support of this investiga-
tion.
r e f e r e n c e s
[
[
[
1] Djerassi C, Miramontes L, Rosenkranz G, Sondheimer F.
Steroids. 54. Synthesis of 19-nor-17-alpha-ethynyl-
testosterone and 19-nor-17-alpha-methyltestosterone. J Am
Chem Soc 1954;76:4092–4.
2] Gorog S. Estimation of impurity profiles. In: Sandor Gorog,
editor. Steroid analysis in the pharmaceutical industry;
hormonal steroids, sterols, vitamin D cardic glycosides.
Chichester, England: Ellis Horwood; 1989. p. 201–6.
3] Nagoshi H, Kinugasa K. In-process control in steroid
synthesis. In: Sandor Gorog, editor. Steroid analysis in the
pharmaceutical industry; hormonal steroids, sterols,
vitamin D cardic glycosides. Chichester, England: Ellis
Horwood; 1989. p. 253–63.
1
.020 [8]. Where the specific gravity is greater than 1.020,
an adjustment is made to raise the threshold. The report-
ing threshold for 19-NA for females was reduced from 5 to
2
ng/mL [8] in 2004. All the tablets analyzed contained mea-
surable amounts of 19-noradrostenedione, an anabolic steroid
prohibited in sport by WADA, the highest amounts found
being 1.01 ± 0.01 ␮g (mean ± S.E.M., n = 5) per tablet in those
containing 5 mg of norethisterone or norethisterone acetate
[
4] Norethisterone Monograph. British Pharmacopoeia
Commission. British pharmacopoeia. London: Stationery
Office; 2005.
(
(
0.02%, w/w) and 0.5 ± 0.01 ␮g (mean ± S.E.M., n = 3) per tablet
[5] Norethisterone Monograph British Pharmacopoeia
Commission. British pharmacopoeia. London: Stationery
Office; 2007.
0.05%, w/w) in oral contraceptive or HRT tablets, contain-
ing 0.35–1.5 mg of norethisterone or norethisterone acetate.
These two products were used in subsequent administra-
tion studies [9]. The proportion of 19-norandrostenedione
in the tablets tested in this study did not exceed the 0.1%
limit specified by the British Pharmacopoeia for this impu-
rity. A trace amount of this impurity is of no pharmacological
consequence but it needs to be considered from an anti-
doping perspective. Catlin et al. found that the ingestion of
as little as 10 ␮g of 19-norandrostenedione resulted in the
excretion of urinary 19-norandrosterone concentrations of
[
6] Norethisterone Monograph British Pharmacopoeia
Commission. British pharmacopoeia. London: Stationery
Office; 2008.
[
7] Wilds AL, Nelson NA. The facile synthesis of
19-nortestosterone and 19-norandrostenedione from
estrone. J Am Chem Soc 1953;75:5366–9.
[8] WADA Technical Document. TD2004NA—Reporting
Norandrosterone Findings. Version Number: 1.0, Effective
Date: August 13, 2004: http://www.wada-ama.org/
rtecontent/document/nandrolone aug 04.pdfI.
[
9] Walker CJ, Cowan DA, James VHT, Lau JCY, Kicman AT.
Doping in Sport 3. Investigating the contribution of
norethisterone and 19-norandrostenedione metabolism to
urinary 19-norandrosterone. Steroids; this issue.
2
.8–48.9 ng/mL 2 h post-administration [10]. Our finding of
amounts up to 1.01 ␮g of 19-norandrostenedione raised issues
concerning whether this impurity in norethisterone tablets
significantly contributes to urinary 19-norandrosterone con-
centrations that exceed the WADA threshold and indeed
whether the 19-norandrosterone detected originates solely
from metabolism of this impurity rather than from norethis-
terone.
Whilst it is recommended to the athlete that they avoid
taking any dietary or herbal preparations [11,12] where there
may be a risk of ingesting trace amounts of anabolic steroids,
including prohormones such as 19-norandrostenedione [13],
it would be inappropriate in our opinion to advise athletes
to avoid pharmaceutical preparations of norethisterone for
medicinal purposes. Further investigations were undertaken
to evaluate the significance of our findings with respect to the
[10] Catlin DH, Leder BZ, Ahrens B, Starcevic B, Hatton CK, Green
GA, et al. Trace contamination of over-the-counter
androstenedione and positive urine test results for a
nandrolone metabolite. JAMA 2000;284:2618–21.
11] Nandrolone progress report to the UK Sports Council from
the Expert Committee on Nandrolone. January 2000; London:
http://www.uksport.gov.uk/assets/File/Generic Template
Documents/Drug Free Sport/Nandrolone Review 180506.pdf.
12] Nandrolone progress report to the UK Sports Council from
the Expert Committee on Nandrolone—February 2003. Int J
Sports Med 2003;24:620–6.
[
[
[
13] Geyer H, Parr MK, Mareck U, Reinhart U, Schrader Y,
Schanzer W. Analysis of non-hormonal nutritional
supplements for anabolic-androgenic steroids—results of an
international study. Int J Sports Med 2004;25:124–9.