The Accumulation And Depletion Of Salbutamol In Chinese Simmental Beef Cattle

The aim of this study was to evaluate the accumulation of salbutamol and its metabolite residues in plasma, urine, and hair, and the distribution in tissues, such as liver, kidney, heart, eye, muscle, lung et al. in order to providing reliable supervision targets for illegal use of salbutamol in beef cattle. The study including three experiments as follows:Trial one: three heifers(516.7 ± 21.9 kg) were given a single oral dose of salbutamol(0.15 mg/kg BW). After treatment, plasma, urine and hair samples were collecting, and the concentrations of salbutamol in samples were measured with UPLC-MS/MS. The results showed that the concentrations of salbutamol were significantly higher in hydrolyzed samples than in the unhydrolyzed samples(P < 0.01); the peak concentrations of salbutamol occurred in plasma 0.3 ng/mL(before hydrolysis) and 32.6 ng/mL(after hydorlysis) at 12 h after dose; the peak salbutamol concentrations in the urine were observed on 0 d(50.2 ng/mL before hydrolysis) and 1 d(3582.1 ng/mL after hydrolysis) following it oral administration; salbutamol concentrations in plasma and urine were below the limit of quantitation on withdrawal day 2 and 5 after dose, respectively; the concentrations of salbutamol in the black and white hair 1 d after its administration were 1.7 and 1.0 ng/g, respectively. The results indicated that salbutamol decreased rapidly in plasma and urine, and the primary forms of salbutamol in the plasma and urine are its conjugates.Trial two: six red-white pied Chinese Simmental beef cattle(311 ± 26.05 kg) which were randomly divided into two groups, and were orally administered with salbutamol at two dose of 0.15, 0.45 mg/kg BW/d for 21 consecutive days, and with a withdrawal time 70 days. Plasma, urine and hair samples were collected during and after treatment, and the concentrations of salbutamol were determined with UPLC-MS/MS, and the metabolites of salbutamol in plasma and urine were identify with UHPLC-Q-TOF MS. The results showed that(1) there were accumulation of salbutamol or its metabolites seems to occur in the plasma during the treatment period, and the concentrations of salbutamol in plasma were decreased rapidly, and below the limits of detection on withdrawal time 7 day(low dose group) and 14 day(high dose group), respectively; salbutamol concentrations were significantly higher in hydrolyzed plasma samples than in unhydrolyzed plasma samples(P < 0.0001), in addition to the parent drug, there was one metabolite of salbutamol in plasma.(2) Unlike plasma, salbutamol concentrations in urine were accumulated with the treatment time, the peak concentration were occurred on treatment day 21 at levels 1654.4 ng/mL(low dose group) and 2444.4 ng/mL(high dose group), then decreased rapidly, and were below the limit of quantitation on withdrawal day 28; salbutamol concentrations were significantly higher in hydrolyzed urine samples than in unhydrolyzed urine samples; there are 6 metabolites of salbutamol in urine samples.(3) Salbutamol concentrations in hair were accumulated with treatment time, and were reached highest levels on treatment day 14(325.77 ng/g in high dose group and 442.55 ng/g in low dose group of red hair) on withdrawal day 14(160.92 ng/g in high dose group and 33.81 ng/g in low dose group of white hair), then the concentrations of salbutamol decreased slowly in hair, and was sill detectable on withdrawal day 70; the concentrations of salbutamol in red hair were significantly higher(P = 0.0068) than that in white hair on the same sampling day.Trial three: Six Chinese Simmental beef cattle(265.67 ± 9.5 kg) were given an orally administered with salbutamol at a dose of 0.15 mg/kg BW/d for 21 consecutive days. On withdrawal days 0 and 14, three cattle were slaughtered for collecting tissues, such as liver, kidney, muscle, fat, eye, spleen, and lung et al. and salbutamol concentrations were determined with UPLC-MS/MS, and the metabolites of salbutamol in liver and kidney were identified with UHPLC-Q-TOF MS. The results showed that salbutamol could be detected in all tissues on withdrawal day 0, and the highest levels of salbutamol observed in liver(53.69 ng/g before hydrolysis and 547.52 ng/g after hydrolysis), and followed by kidney, fat, aqueous humor, eye muscles, bile, small intestine, spleen, rumen wall, large intestine, lung, muscle; on withdrawal day 14, the concentrations of salbutamol in eye muscles and large intestine were increased, while other tissues were decreased; there are 1 metabolites of salbutamol in liver and 3 metabolites of salbutamol in kidney, and the concentrations of salbutamol in hydrolyzed liver and kidney samples were higher than in unhydrolyzed samples, suggesting that the primary forms of salbutamol in liver and kidney are its metabolites.