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Accurate measurement of androgen after androgen esters: problems created by ex vivo esterase effects and LC-MS/MS interference.

ABSTRACT: BACKGROUND:Ex vivo androgen prodrug conversion by blood esterases after oral androgen ester administration may result in an overestimation of the measured blood androgens. OBJECTIVE:We investigated whether blood collection tubes with esterase inhibitors decreased the conversion of testosterone undecanoate (TU) and dimethandrolone undecanoate (DMAU) to their active metabolites, testosterone (T), and dimethandrolone (DMA), providing a more accurate assessment of circulating T/DMA levels. METHODS:Blood was collected in tubes with/without esterase inhibitors from: (i) four healthy and four hypogonadal men receiving no androgens and spiked ex vivo with TU/DMAU; (ii) four men taking oral TU (Andriol® ); and (iii) eight hypogonadal men dosed with oral 316 mg TU and 15 healthy men with 200 mg DMAU. T/DMA levels were measured by LC-MS/MS. RESULTS:Sodium fluoride (NaF, an esterase inhibitor) decreased measured T levels by 14.2% in men not receiving TU. Increasing amounts of TU/DMAU added to blood collected into plain tubes resulted in a concentration-dependent overestimation of T/DMA that was reduced by collecting blood into NaF tubes (by 30-85%), and keeping samples at 4 °C and minimizing time prior to centrifugation. After oral TU/DMAU administration to men, when TU/DMAU levels were >15/10 ng/mL, respectively, blood collected in NaF tubes yielded lower measured T concentrations by 15-30% and DMA by 22% due to an additional inhibitory effect of NaF on blood esterases. CONCLUSION:NaF directly lowers plasma T/DMA levels measured by LC-MS/MS and also inhibits blood esterase activity. Overestimation of T/DMA in blood collected in tubes without NaF after oral TU/DMAU administration is important for pharmacokinetics studies in drug development clinical trials but may have limited impact in clinical practice/utilization because the differences between measured and true androgen values are modest and the wide therapeutic androgen efficacy ranges obviate the need for highly accurate androgen measurements during therapy.

SUBMITTER: Ceponis J

PROVIDER: S-EPMC6519384 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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Accurate measurement of androgen after androgen esters: problems created by ex vivo esterase effects and LC-MS/MS interference.

Ceponis J J Swerdloff R R Leung A A Hull L L Bai F F Longstreth J J Dudley R R Danoff T T Wang C C

Andrology 20181021 1

<h4>Background</h4>Ex vivo androgen prodrug conversion by blood esterases after oral androgen ester administration may result in an overestimation of the measured blood androgens.<h4>Objective</h4>We investigated whether blood collection tubes with esterase inhibitors decreased the conversion of testosterone undecanoate (TU) and dimethandrolone undecanoate (DMAU) to their active metabolites, testosterone (T), and dimethandrolone (DMA), providing a more accurate assessment of circulating T/DMA le ...[more]

PMID: 30345711

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Dataset Information

Accurate measurement of androgen after androgen esters: problems created by ex vivo esterase effects and LC-MS/MS interference.

Publications

Accurate measurement of androgen after androgen esters: problems created by ex vivo esterase effects and LC-MS/MS interference.

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