Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Urinary Excretion Kinetics of Salbutamol and Its Sulfoconjugated Main Metabolite After Oral and Inhalative Administration of Racemic Salbutamol or Levosalbutamol

Version 1 : Received: 24 February 2023 / Approved: 27 February 2023 / Online: 27 February 2023 (06:27:43 CET)

How to cite: Jendretzki, A.L.; Harps, L.C.; Sun, Y.; Bredendiek, F.; Bureik, M.; Girreser, U.; De la Torre, X.; Botrè, F.; Parr, M.K. Urinary Excretion Kinetics of Salbutamol and Its Sulfoconjugated Main Metabolite After Oral and Inhalative Administration of Racemic Salbutamol or Levosalbutamol. Preprints 2023, 2023020447. https://doi.org/10.20944/preprints202302.0447.v1 Jendretzki, A.L.; Harps, L.C.; Sun, Y.; Bredendiek, F.; Bureik, M.; Girreser, U.; De la Torre, X.; Botrè, F.; Parr, M.K. Urinary Excretion Kinetics of Salbutamol and Its Sulfoconjugated Main Metabolite After Oral and Inhalative Administration of Racemic Salbutamol or Levosalbutamol. Preprints 2023, 2023020447. https://doi.org/10.20944/preprints202302.0447.v1

Abstract

It was the aim of this study to compare the ratio of salbutamol and its major metabolite salbutamol-4’-O-sulfate as well as the quantity excreted renally after oral and inhalative administration. Additionally, the excretion pattern after application of racemic salbutamol opposed to the pure enantiomer levosalbutamol was evaluated. For quantitation of the sulfonated metabolite of salbutamol, reference material was synthesized and characterized by NMR and HRMS. Urine samples were analyzed by ultrahigh performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Salbutamol is mainly metabolized by sulfotransferase 1A3 (SULT1A3), which is most abundantly found in the jejunum. A high first pass effect occurs upon oral administration, which leads to a higher amount of salbutamol-4’-O-sulfate in urine compared to unchanged salbutamol excreted within the first hour post administration. Thus, when administered orally, the proportion of metabolite to total salbutamol was higher than for inhalative administration in the early urinary excretion. Levosalbutamol is the favored enantiomer of SULT1A3 and therefore metabolized at a higher rate whereas racemic salbutamol shows a reduced proportion between metabolite and parent compound. The amount of sulfoconjugate was found higher than that of the parent compound for all urine samples except for those excreted in the first hour after inhalative administration.

Keywords

salbutamol; metabolism; excretion rates; salbutamol-4’-O-sulfate; bioanalysis; biosynthesis; SULT1A3

Subject

Medicine and Pharmacology, Pharmacology and Toxicology

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