Identification of Buctopamine and Mebuctopamine, a β₂ Receptor Agonist and Its Metabolite, in Swine Hair and Feed Additives

Abstract

4-[2-(t-Butylamino)-1-hydroxyethyl]phenol (buctopamine, 4), a new β receptor agonist (β-agonist), was found to be an adulterant in feed additives for swine in Taiwan, where using β-agonists in food-production animals is prohibited. Buctopamine and its metabolite, 4-[2-(t-butylamino)-1-hydroxyethyl]-2-methoxyphenol (mebuctopamine, 2), were detected in swine hair specimens. Authentic compounds 2 and 4 were synthesized with 98.6% and 97.7% purity, respectively, as reference standards for analysis, and both compounds were more hydrophilic than ractopamine and clenbuterol. In a preliminary pharmacological evaluation, compounds 2 and 4 exhibited moderate human β receptor binding affinity and did not show significant affinities for the human α, α, β, and β receptors. After addition of compounds 2-4 into the β-agonist library, a multiresidue analysis of 26 β-agonists by using triple quadrupole LC/MS/MS for routine screening conducted by regulatory authorities was established, in which the common limits of quantification for the 26 β-agonists in swine feed and hair are 10 and 25 ng/g, respectively. In addition, the illegal use of buctopamine (4) has been effectively prevented. The results of this study are also useful for controlling the illegal use of new β-agonists in food-production animals.

Four Hapten Spacer Sites Modulating Class Specificity: Nondirectional Multianalyte Immunoassay for 31 β-Agonists and Analogues

“…In the United States, only ractopamine and zilpaterol were approved as feed additives for cattle and swine by the FDA, and other compounds are banned in animal products . However, all β-agonists have been banned for animal products in the European Union (EU) and China.…”

“…However, all β-agonists have been banned for animal products in the European Union (EU) and China. Ractopamine, clenbuterol, salbutamol, zilpaterol, cimaterol, terbutaline, and tulobuterol were officially banned and are most often found being illegally used in China. , For purpose of investigating the impact of hapten structure on the antibody specificity, 54 compounds were used for the evaluation of cross-reactivity. These compounds included the most common β-agonists and their analogues, e.g., clenbuterol, ractopamine, zilpaterol, clenhexerol, and 3-dehydroxy salbutamol.…”

“…In the United States, only ractopamine and zilpaterol were approved as feed additives for cattle and swine by the FDA, and other compounds are banned in animal products. 32 However, all β-agonists have been banned for animal products in the European Union (EU) and China. Ractopamine, clenbuterol, salbutamol, zilpaterol, cimaterol, terbutaline, and tulobuterol were officially banned and are most often found being illegally used in China.…”

“…(I) t-butylnorsynephrine ( 16 The yellow contour near C-2′ implied that a huge steric field on the tertamyl would decrease the cross-reactivity. Thus, it was reasonable that those compounds with bulky rings at C-2′ (e.g., arformoterol (29) (CR < 0.1%), olodaterol (31), indacaterol (32), fenspiride (20), reproterol (22), ractopamine (24), and ritodrine (25) (CR, ND)) demonstrated very low crossreactivity and even no recognition.…”