Analysis ofβ‐agonists in urine and tissues by capillary gas chromatography‐mass spectrometry:In vivostudy of salbutamol disposition in calves

Abstract

The fate of salbutamol sulphate given orally has been investigated in calves. The urinary excretion rate and the tissue distribution of this beta-agonistic drug were studied by capillary gas chromatography coupled to low resolution mass spectrometry (GC-LRMS) under electron impact (EI) ionization mode, using an hexadeuterated salbutamol analogue as the internal standard. The parent drug and metabolites were extracted via solid phase extraction (SPE) mixed-phase-containing disposable columns and analysed as their trimethylsilyl derivatives. A more efficient clean-up had to be carried out for tissue samples. An acidic precipitation followed by a liquid-liquid extraction were therefore performed before the SPE. Moreover, the problem of tissue digestion was elucidated by means of an ultrasonic probe. Samples were also analysed before and after enzymic hydrolysis using purified beta-glucuronidase and a mixture of beta-glucuronidase and arylsulphatase, to obtain evidence of phase II conjugation mechanisms. Both free salbutamol and conjugated metabolites were detected in urine and tissue samples. Except for liver or kidney, salbutamol was rapidly cleared from most tissues after a withdrawal period. The possible excretion of some phase I metabolites was also investigated, using further analyses under positive chemical ionization LRMS and high resolution mass spectrometry (HRMS).

Broad screening and identification of β-agonists in feed and animal body fluid and tissues using ultra-high performance liquid chromatography-quadrupole-orbitrap high resolution mass spectrometry combined with spectra library search

“…These methods include liquid chromatography (Chang, Chou, & Hwang, 2005;Meng et al, 2012;Turberg, Macy, Lewis, & Coleman, 1994), gas chromatography (Bocca, Fiori, Cartoni, & Brambilla, 2003), liquid chromatography tandem mass spectrometry (LC-MS/MS) (Shishani, Chai, Jamokha, Aznar, & Hoffman, 2003;Wu, Liu, & Peng, 2014), gas chromatography-mass spectrometry (Montrade, Lebizec, Monteau, & Andre, 1995;Wang, Li, Zhang, & Shen, 2006), enzyme-linked immunoassay (Hahnau & Julicher, 1996;Harkins, Woods, Lehner, Fisher, & Tobin, 2001;Pinheiro et al, 2008), colloidal gold test strip (Khamta, Pattarawarapan, Nangola, & Tayapiwatana, 2009;Zhang et al, 2009), surface plasmon resonance immunosensors (Traynor, Crooks, Bowers, & Elliott, 2003), and electrochemical immunosensors (He, Wang, Zhang, & Yang, 2009). Table 1 Chemical formula, accurate mass, retention time and characteristic fragment ions of 32 b-agonists.…”

Identification of the major metabolites of (R)‐salbutamol in human urine, plasma and feces using ultra high performance liquid chromatography coupled with quadrupole time‐of‐flight mass spectrometry

“…The investigation of drug metabolism is of great significance to the evaluation of the efficacy and safety of clinical drugs. Some early researches reported the major metabolites of salbutamol in serum, urine, and internal tissues of animals such as calves , beef cattle , swines , rats, rabbits, and dogs . However, there are few reports on the metabolites of salbutamol in humans.…”

Acetylcholine-induced aortic relaxation studied in salbutamol treated rats

“…As previous studies have suggested low oral bioavailability of salbutamol in rats (Montrade et al, 1995;Smith, 1998), we treated our animals with a highly concentrated solution of salbutamol (5 mg/100 ml of drinking water). Considering that treated animals consumed an average of 63 ml/day of drinking water, we estimated that the animals received a daily dose of 3.15 mg salbutamol per animal, or between about 8 and 9.5 mg/kg.…”