Utility of isolated hepatocytes and radio-HPLC-MSn for the analysis of the metabolic fate of 19-nortestosterone laurate in cattle†

Coldham, N. G.; Biancotto, Giancarlo; Montesissa, Clara; Howells, L. G.; Sauer, M. J.

doi:10.1039/a805109g

Cited by 7 publications

(2 citation statements)

References 12 publications

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“…In the present preliminary application of LC-MS, attempts to identify the major bile and urine metabolites were hindered by poor molecular ion formation produced by the estranes, which was possibly exacerbated by interference from matrix co-extractives. Some of the problems encountered have been addressed in parallel studies using hepatocytes to investigate biotransformation by the liver in steers; 19 these studies used positive ion LC-APCI-MS 2 and comparison with reference standards indicated biotransformation to 4-estren-17a-ol-3-one, 4-estrene-3,17-dione (major metabolite after 1 h), n-hydroxy-4-estrene-3,17-dione, n-hydroxy-4-estren-17-ol-3-one, 5b-estran-3a-ol-17-one and 5b-estrane-3a,17b-diol (major metabolite after 4 h of incubation) and (by ESI-MS 2 ) their respective glucuronide conjugates.…”

Section: Urine and Bile Metabolite Profilesmentioning

confidence: 99%

Residues and metabolism of 19-nortestosterone laurate in steers†

Sauer¹,

Howells²,

Bellworthy³

et al. 1998

Analyst

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The illegal use of nandrolone) and its esters in livestock, for growth promotion purposes, has been widely reported in the European Union. The target residues for surveillance of abuse in bovine urine and bile samples are 17a-and 17b-19NT, although this choice of target residues is not based on in vivo radiotracer biotransformation data. In this study, four steers were administered [ 3 H 2 ]-and [ 2 H 3 ] 17b-19NT laurate (2 mg kg 21 body mass) by intramuscular injection and blood, urine, faeces and bile samples were taken for 30 d until slaughter, after which tissues were sampled for total residue analysis. Total plasma radiolabelled residues reached a maximum of 56.3 ± 15.9 pmol ml 21 at 36 h and were still appreciable (13.3 ± 1.6 pmol ml 21 ) 30 d after treatment. Throughout the study period, total residue concentrations in bile (about 2-16 nmol ml 21 ), urine and faeces (0.5-3 nmol ml 21 or g 21 ) were higher than in other tissues sampled at slaughter. At slaughter there was evidence of residue accumulation in pigmented eye tissue (33.1 ± 6.1 pmol g 21 ) and in white (13.4 ± 3.4 pmol g 21 ) and black hair (28.9 ± 8.9 pmol g 21 ). Evaluation of radio-HPLC profiles of urine and bile extracts generally indicated that 19NT and 19NT laurate residues were present in relatively small amounts among a complex mixture of metabolites. GC-MS analysis of glucuronidase-hydrolysed bile extracts indicated that the major metabolites were 5b-estrane-3a,17a-diol, 5a-estrane-3b,17a-diol, 5a-estran-3a-ol-17-one (norandrosterone) and estra-1,3,5(10)-triene-3,17a-diol (17a-estradiol).

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Section: Urine and Bile Metabolite Profilesmentioning

confidence: 99%

Residues and metabolism of 19-nortestosterone laurate in steers†

Sauer¹,

Howells²,

Bellworthy³

et al. 1998

Analyst

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show abstract

“…GC/MS was used as a detection method, with a LOD of 0.02 ng/ml [28]. Structural modifications of nortestosterone, such as esterification of the 17␤-position, allow the compound to be administered via intramuscular injection [29][30][31][32].…”

Section: Introductionmentioning

confidence: 99%