A urinary cysteine-halothane metabolite: validation and measurement in children

An attempt was made in children to identify a urinary halothane-cysteine conjugate which had been described previously in adult patients following administration of halothane. If this conjugate was found it would indicate that a reductive metabolite of halothane binds covalently with the sulphydryl-containing amino acid, cysteine, a reaction which could lead to hepatic injury. The potential halothane-cysteine conjugate, N-acetyl-S-(2-bromo-2-chloro-1,1-difluoroethyl)-L-cysteine (acetyl BCFEC), was prepared and the identity of the compound established using hydrogen-1 and carbon-13 NMR spectroscopy and methane chemical ionization mass spectrometry. A measurement technique for acetyl BCFEC was developed using HPLC with u.v. detection at 200 nm. In six children after halothane anaesthesia, one child being studied twice, urine was collected for up to 1 week and analysed for acetyl BCFEC. Little or no acetyl BCFEC was detected in any of the 43 urine samples tested, indicating that in children it is not a significant urinary metabolite of halothane.