Physicochemical Properties
| Molecular Formula | C18H23NO3 |
| Molecular Weight | 301.38 |
| Exact Mass | 301.167 |
| CAS # | 97825-25-7 |
| PubChem CID | 56052 |
| Appearance | Typically exists as solid at room temperature |
| Density | 1.2±0.1 g/cm3 |
| Boiling Point | 520.5±50.0 °C at 760 mmHg |
| Melting Point | 165-167ºC |
| Flash Point | 165.3±20.7 °C |
| Vapour Pressure | 0.0±1.4 mmHg at 25°C |
| Index of Refraction | 1.609 |
| LogP | 1.65 |
| Hydrogen Bond Donor Count | 4 |
| Hydrogen Bond Acceptor Count | 4 |
| Rotatable Bond Count | 7 |
| Heavy Atom Count | 22 |
| Complexity | 297 |
| Defined Atom Stereocenter Count | 0 |
| SMILES | OC1C=CC(CCC(C)NCC(C2C=CC(O)=CC=2)O)=CC=1 |
| InChi Key | YJQZYXCXBBCEAQ-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C18H23NO3/c1-13(2-3-14-4-8-16(20)9-5-14)19-12-18(22)15-6-10-17(21)11-7-15/h4-11,13,18-22H,2-3,12H2,1H3 |
| Chemical Name | 4-[3-[[2-hydroxy-2-(4-hydroxyphenyl)ethyl]amino]butyl]phenol |
| HS Tariff Code | 2934.99.9001 |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| Targets | pig β1AR ~25 nM (Kd) pig β2AR ~25 nM (Kd) |
| ln Vivo | Pig muscle protein accretion is reliably increased by ractopamine[3]. |
| ADME/Pharmacokinetics |
Absorption, Distribution and Excretion /The authors/ investigated the detection, confirmation, and metabolism of the beta-adrenergic agonist ractopamine administered as Paylean to the horse. ... Based on the quantitation ions for ractopamine standards extracted from urine, standard curves showed a linear response for ractopamine concentrations between 10 and 100 ng/mL with a correlation coefficient r > 0.99, whereas standards in the concentration range of 10-1000 ng/mL were fit to a second-order regression curve with r > 0.99. ... Urine concentration of parent ractopamine 24 h post-dose was measured at 360 ng/mL by GC-MS after oral administration of 300 mg. Urinary metabolites were identified by electrospray ionization (+) tandem quadrupole mass spectrometry and were shown to include glucuronide, methyl, and mixed methyl-glucuronide conjugates In a bioavailability study that complied with good laboratory practice (GLP), groups of five male and five female rats were given [14C]ractopamine as a single oral dose at 0.5, 2.0, or 20 mg/kg bw by gavage. The amount of radiolabel was quantified in samples of plasma and whole blood collected for 24 hr after dosing. Comparison of the area under the curve (AUC) of concentration-time for plasma and whole blood indicated that the bioavailability of (14)C-ractopamine was proportional to dose for males and females at doses up to 2.0 mg/kg bw. Increasing the dose to 20 mg/kg bw resulted in an increase in AUC versus dose in males and, to a more pronounced degree, in females. The absolute bioavailability of (14)C-ractopamine in rats cannot be determined from the results of this study since (14)C-ractopamine was not administered intravenously for comparison of oral and intravenous AUC values. Experiments were conducted to determine the total residues remaining in ocular tissues of cattle and turkeys after oral administration of (14)C-ractopamine HCl. Twelve cattle were intraruminally dosed with 0.9 mg /kg/d of (14C-)ractopamine HCl for 7 d. Four cattle each were slaughtered with withdrawal periods of 48, 96, and 144 hr. Radioactive residues were not detectable in whole-eye homogenates from the cattle. Eight male and eight female turkeys per treatment received either 7.5, 22.5, or 30 ppm dietary (14)C-ractopamine HCl (0.33, 1.02, and 1.36 mg/kg/d; treatment groups 1, 2, and 3, respectively) for 7 d, and the birds were slaughtered with a 0-d withdrawal period. Eyes were dissected into retina/choroid/schlera (RCS), cornea/iris (CI), and aqueous humor (AH) fractions. Residues in RCS, CI, and AH of treatment 1 turkeys were not detectable. Residues in AH were < 0.02 ppm in treatment groups 2 and 3. Mean residues in RCS ranged from 0.15 to 0.26 ppm, and mean CI residues ranged from <0.09 to 0.17 ppm for treatment groups 2 and 3, respectively. Ractopamine HCl is a beta-adrenergic leanness-enhancing agent recently approved for use in swine. Depletion of ractopamine in tissues, and elimination of ractopamine and its metabolites in urine, is of interest for the detection of off-label use. The objectives of this study were to measure the residues of ractopamine in livers and kidneys of cattle (n = 6), sheep (n = 6), and ducks (n = 9) after treatment with dietary ractopamine for seven (sheep, ducks) or eight (cattle) consecutive days and to measure the depletion of ractopamine from urine of cattle and sheep. Two cattle and sheep and three ducks were each slaughtered with withdrawal periods of 0, 3, and 7 day. Urine samples were collected daily from cattle and sheep. Tissue ractopamine concentrations were determined using the regulatory method (FDA approved) for ractopamine in swine tissues. Ractopamine residues in urine samples were measured before and after hydrolysis of conjugates. Analysis was performed with HPLC using fluorescence detection after liquid- (hydrolyzed samples) and(or) solid-phase extraction. No residues were detected in duck tissues. Liver residues in sheep averaged 24.0 and 2.6 ppb after 0- and 3-day withdrawal periods, respectively. Sheep liver residues after a 7-day withdrawal period were less than the limit of quantification (2.5 ppb). Sheep kidney residues were 65.1 and undetectable at 0- and at 3- and 7-day, withdrawal periods, respectively. Cattle liver residues were 9.3, 2.5, and undetectable after 0-, 3-, and 7-day withdrawal periods, respectively; kidney residues were 97.5, 3.4, and undetectable at the same respective withdrawal periods. Concentrations of parent ractopamine in sheep urine were 9.8+ or - 3.3 ppb on withdrawal d 0 and were below the LOQ (5 ppb) beyond the 2-day withdrawal period. After the hydrolysis of conjugates, ractopamine concentrations were 5,272 + or - 1,361 ppb on withdrawal d 0 and 178 + or - 78 ppb on withdrawal d 7. Ractopamine concentrations in cattle urine ranged from 164+ or - 61.7 ng/mL (withdrawal d 0) to below the LOQ (50 ppb) on withdrawal day 4. After the hydrolysis of conjugates in cattle urine, ractopamine concentrations were 4,129+ or - 2,351 ppb (withdrawal day 0) to below the LOQ (withdrawal d 6). These data indicate that after the hydrolysis of conjugates, ractopamine should be detectable in urine of sheep as long as 7 day after the last exposure to ractopamine and as long as 5 day after withdrawal in cattle. For more Absorption, Distribution and Excretion (Complete) data for RACTOPAMINE (16 total), please visit the HSDB record page. Metabolism / Metabolites In urine, only a minor fraction of radioactivity recovered was parent ractopamine. Swine excreted about 4-16% of the parent compound in the urine after a single oral dose of ractopamine. After repeated doses, the amount of unchanged drug increased to 36-85% of total radioactivity in the urine collected on day 4 of a 4-day dosing regimen. In rats injected with (14)C-ractopamine at 9 mg/kg bw intraperitoneally, parent drug represented 22.6% of total urinary radioactivity while only 1.9% of radioactivity was associated with unchanged ractopamine after an oral dose of 9.9 mg/kg bw. The greater proportion of parent drug in the urine after parenteral administration than after oral administration suggests that liver and intestine play an important role in the biotransformation of ractopamine after oral administration. Therefore, although well absorbed from the gastrointestinal tract, the systemic availability of parent ractopamine is reduced, owing to a significant first-pass metabolism. In the bile of rats dosed orally with (14)C-ractopamine, at least seven different crude metabolite fractions were partitioned chromatographically. Four of the crude metabolite fractions representing 76% of biliary radioactivity were isolated and identified with a sulfate-ester/glucuronic acid diconjugate of ractopamine as the main metabolite (46% of total biliary radioactivity). A further 6% of radioactivity was identified as a monosulfate conjugate and 25% as monoglucuronides of ractopamine. The site of sulfation was established at the C-10' phenol (aromatic ring attached to carbinol). The sulfate conjugation was not stereospecific. The major site of glucuronidation was the C-10 phenol (phenol attached to the nitrogen substituent). After a withdrawal of 6 hr (rats, dogs) or 12hr (swine, cattle), unchanged ractopamine represented 40, 14, 52, and 13-16% of the total extractable and identifiable residues in the rat, dog, pig, and cattle livers, respectively, and 21, 29, 28-30, and 14% in the kidneys, respectively. After a withdrawal of 24 hr and 72 hr, parent ractopamine represented 14.1% and 3.6% in liver, and 27.5% and 3% of total residues in kidney, respectively, in swine. The remaining residue was found to comprise conjugates of ractopamine. The chromatographic profiles of the (14)C-labelled residue extracts of rat, dog, pig, and cattle liver were qualitatively similar. The laboratory animals had generally a higher percentage of metabolites as residues. Studies in rats and dogs showed that urine from animals dosed with (14)C-ractopamine contained the same four glucuronide metabolites of ractopamine as in pigs. It is concluded that the dogs and rats used in the toxicological studies were exposed to the same metabolites as those found in the edible tissues of pigs and cattle. In studies in rats, dogs, pigs, and cattle fed (14)C-ractopamine, a fourth metabolite was identified as a glucuronic acid diconjugate. The conjugation of the hydroxyl groups in both the aromatic ring attached to the carbinol and the phenol attached to the nitrogen substituent was not stereospecific. For more Metabolism/Metabolites (Complete) data for RACTOPAMINE (8 total), please visit the HSDB record page. Biological Half-Life Elimination 1/2 life = 6-7 hours; [HSDB] The elimination half-life was about 6-7 hr. The results of a study in six healthy male human volunteers receiving a single oral dose of 40 mg of ractopamine hydrochloride indicate a similar profile of pharmacokinetics and biotransformation in humans and animals. ... The half-life in plasma was about 4 hr. |
| Toxicity/Toxicokinetics |
Interactions An 8-wk study of the effects of CLA, rendered animal fats, and ractopamine, and their interactive effects on growth, fatty acid composition, and carcass quality of genetically lean pigs was conducted. Gilts (n = 228; initial BW of 59.1 kg) were assigned to a 2 x 2 x 3 factorial arrangement consisting of CLA, ractopamine, and fat treatments. The CLA treatment consisted of 1% CLA oil (CLA-60) or 1% soybean oil. Ractopamine levels were either 0 or 10 ppm. Fat treatments consisted of 0% added fat, 5% choice white grease (CWG), or 5% beef tallow (BT). The CLA and fat treatments were initiated at 59.1 kg of BW, 4 wk before the ractopamine treatments. The ractopamine treatments were imposed when the gilts reached a BW of 85.7 kg and lasted for the duration of the final 4 wk until carcass data were collected. Lipids from the belly, outer and inner layers of backfat, and LM were extracted and analyzed for fatty acid composition from 6 pigs per treatment at wk 4 and 8. Feeding CLA increased (P < 0.02) G:F during the final 4 wk. Pigs fed added fat as either CWG or BT exhibited decreased (P < 0.05) ADFI and increased (P < 0.01) G:F. Adding ractopamine to the diet increased (P < 0.01) ADG, G:F, and final BW. The predicted carcass lean percentage was increased (P < 0.05) in pigs fed CLA or ractopamine. Feeding either 5% fat or ractopamine increased (P < 0.05) carcass weight. Adding fat to the diets increased (P < 0.05) the 10th rib backfat depth but did not affect predicted percent lean. Bellies of gilts fed CLA were subjectively and objectively firmer (P < 0.01). Dietary CLA increased (P < 0.01) the concentration of saturated fatty acids and decreased (P < 0.01) the concentration of unsaturated fatty acids of the belly fat, both layers of backfat, and LM. Ractopamine decreased (P < 0.01) the i.m. fat content of the LM but had relatively little effect on the fatty acid profiles of the tissues compared with CLA. These results indicate that CLA, added fat, and ractopamine work mainly in an additive fashion to enhance pig growth and carcass quality. Furthermore, these results indicate that CLA results in more saturated fat throughout the carcass. |
| References |
[1]. Stress susceptibility in pigs supplemented with ractopamine. J Anim Sci. 2013;91(9):4180-4187. [2]. Ractopamine increases total and myofibrillar protein synthesis in cultured rat myotubes. J Nutr. 1990;120(12):1677-1683. [3]. S. E. Mills, Biological basis of the ractopamine response, Journal of Animal Science, Volume 80, Issue E-suppl_2, 2002, Pages E28–E32. |
| Additional Infomation |
4-(1-hydroxy-2-{[4-(4-hydroxyphenyl)butan-2-yl]amino}ethyl)phenol is a secondary amino compound that is 4-(2-amino-1-hydroxyethyl)phenol in which one of the hydrogens attached to the nitrogen is replaced by a 4-(p-hydroxyphenyl)butan-2-yl group. It is a polyphenol, a secondary amino compound, a member of benzyl alcohols and a secondary alcohol. See also: Ractopamine Hydrochloride (has salt form). Mechanism of Action The RR-isomer (butopamine) is the stereoisomer with the most activity at the b-adrenoceptor. Butopamine was shown to be a non-selective ligand at the beta1- and beta2-adrenoceptors, but signal transduction is more efficiently coupled through the b2-adrenoceptor than the b1- adrenoceptor. Therefore, the RR-isomer of ractopamine is considered to be a full agonist at the beta2-adrenoceptor and a partial agonist at the beta-adrenoceptor. These results are consistent with the pharmacological characterization of racemic ractopamine in isolated cardiac (atria) and smooth muscle (costo-uterine, vas deferens, trachea), which shows a maximal response at beta2- and a submaximal response at b1-adrenoceptors when compared with the full beta1- and beta2- adrenoceptor agonist isoproterenol. Therapeutic Uses Mesh Heading: Adrenergic beta-agonists MEDICATION (VET): Animal growth promotant MEDICATION (VET): The effects of the beta-agonist ractopamine, approved for use in finishing swine and cattle to improve carcass quality and performance, were examined on two important foodborne pathogens, Escherichia coli O157:H7 and Salmonella. Ractopamine, administered to sheep before and after oral inoculation with E. coli O157:H7, increased (P < 0.01) fecal shedding and tended to increase (P = 0.08) cecal populations of the challenge strain. Pigs receiving ractopamine in the diet and then experimentally infected with Salmonella Typhimurium, had decreased (P < 0.05) fecal shedding and fewer (P = 0.05) liver samples positive for the challenge strain of Salmonella. Pure cultures of E. coli O157:H7 (used in the present sheep study), E. coli O157:H19 (isolated from pigs with postweaning diarrhea), Salmonella Typhimurium (used in the present pig study), and Salmonella Choleraesuis were incubated with varying concentrations of ractopamine to determine if ractopamine has a direct effect on bacterial growth. No differences in growth rate were observed for either strain of E. coli or for Salmonella Typhimurium when incubated with increasing concentrations of ractopamine. The growth rate for Salmonella Choleraesuis was increased with the addition of 2.0 ug ractopamine/ml compared with the other concentrations examined. Collectively, these results indicate that ractopamine may influence gut populations and fecal shedding of E. coli O157:H7 and Salmonella. Because ractopamine is currently approved to be fed to finishing cattle and swine immediately before slaughter, any potential for decreasing foodborne pathogens has exciting food safety implications. MEDICATION (VET): An 8-wk study of the effects of CLA, rendered animal fats, and ractopamine, and their interactive effects on growth, fatty acid composition, and carcass quality of genetically lean pigs was conducted. Gilts (n = 228; initial BW of 59.1 kg) were assigned to a 2 x 2 x 3 factorial arrangement consisting of CLA, ractopamine, and fat treatments. The CLA treatment consisted of 1% CLA oil (CLA-60) or 1% soybean oil. Ractopamine levels were either 0 or 10 ppm. Fat treatments consisted of 0% added fat, 5% choice white grease (CWG), or 5% beef tallow (BT). The CLA and fat treatments were initiated at 59.1 kg of BW, 4 wk before the ractopamine treatments. The ractopamine treatments were imposed when the gilts reached a BW of 85.7 kg and lasted for the duration of the final 4 wk until carcass data were collected. Lipids from the belly, outer and inner layers of backfat, and LM were extracted and analyzed for fatty acid composition from 6 pigs per treatment at wk 4 and 8. Feeding CLA increased (P < 0.02) G:F during the final 4 wk. Pigs fed added fat as either CWG or BT exhibited decreased (P < 0.05) ADFI and increased (P < 0.01) G:F. Adding ractopamine to the diet increased (P < 0.01) ADG, G:F, and final BW. The predicted carcass lean percentage was increased (P < 0.05) in pigs fed CLA or ractopamine. Feeding either 5% fat or ractopamine increased (P < 0.05) carcass weight. Adding fat to the diets increased (P < 0.05) the 10th rib backfat depth but did not affect predicted percent lean. Bellies of gilts fed CLA were subjectively and objectively firmer (P < 0.01). Dietary CLA increased (P < 0.01) the concentration of saturated fatty acids and decreased (P < 0.01) the concentration of unsaturated fatty acids of the belly fat, both layers of backfat, and LM. Ractopamine decreased (P < 0.01) the i.m. fat content of the LM but had relatively little effect on the fatty acid profiles of the tissues compared with CLA. These results indicate that CLA, added fat, and ractopamine work mainly in an additive fashion to enhance pig growth and carcass quality. Furthermore, these results indicate that CLA results in more saturated fat throughout the carcass. For more Therapeutic Uses (Complete) data for RACTOPAMINE (8 total), please visit the HSDB record page. |
Solubility Data
| Solubility (In Vitro) | May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples |
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples. Injection Formulations (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] *Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Oral Formulations Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.3181 mL | 16.5904 mL | 33.1807 mL | |
| 5 mM | 0.6636 mL | 3.3181 mL | 6.6361 mL | |
| 10 mM | 0.3318 mL | 1.6590 mL | 3.3181 mL |