Helen Frankenthaler Foundation

α-Endorphin CAS 59004-96-5

Determination of an endothelin receptor antagonist in human plasma by narrow-bore liquid chromatography and ionspray tandem mass spectrometry

Abstract

A method is described for the determination of a new endothelin receptor antagonist, Bosentan Ro 47-0203, in human plasma using narrow-bore liquid chromatography and ionspray tandem mass spectrometry. After protein precipitation with acetonitrile, the compounds were extracted with dichloromethane at pH 11. The compounds were chromatographed on a 2 mm I.D. reversed-phase column and introduced into the mass spectrometer with an ionspray (pneumatically assisted electrospray) interface at a flow-rate of 170 μl/min without postcolumn splitting. Two different internal standards were used for the assay: either a structural analogue or a deuterated analogue. The limit of quantification was 0.5 ng/ml using a 0.5-ml aliquot of plasma. Concentrations of the drug were determined in the range 0.5–200 ng/ml. The recovery from human plasma was 87%. The new API IIIplus collision cell was about five times more sensitive than the original API III cell. The assay was demonstrated to be sensitive, selective and robust for the analysis of over 1500 samples.

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Cited by (23)

  • Simultaneous determination of bosentan and its three major metabolites in various biological matrices and species using narrow bore liquid chromatography with ion spray tandem mass spectrometric detection 2000, Journal of Chromatography B Biomedical Sciences and Applications
  • Liquid chromatography-mass spectrometry in forensic and clinical toxicology 1998, Journal of Chromatography B Biomedical Applications
  • HPLC Methods for Recently Approved Pharmaceuticals 2005, Hplc Methods for Recently Approved Pharmaceuticals
  • Influence of food intake and formulation on the pharmacokinetics and metabolism of bosentan, a dual endothelin receptor antagonist 2002, Journal of Clinical Pharmacology
  • Multiple-Dose Pharmacokinetics, Safety, and Tolerability of Bosentan, an Endothelin Receptor Antagonist, in Healthy Male Volunteers 1999, Journal of Clinical Pharmacology
  • Pharmacokinetics and pharmacodynamics of the endothelin-receptor antagonist bosentan in healthy human subjects 1996, Clinical Pharmacology and Therapeutics
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