Ractopamine Hydrochloride Suspension

This article is compiled based on the United States Pharmacopeia (USP) – 2025 Edition

Issued and maintained by the United States Pharmacopeial Convention (USP)

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C₁₈H₂₃NO₃.HCl 337.84

Benzenemethanol, 4-hydroxy-α-[[[3-(4-hydroxyphenyl)-1-methylpropyl]amino]methyl]-, hydrochloride;

(±)-all-rac-p-Hydroxy-α-[[[3-(p-hydroxyphenyl)-1-methylpropyl]amino]methyl]benzyl alcohol, hydrochloride CAS RN®: 90274-24-1; UNII:  309G9J93TP.

1 DEFINITION

Ractopamine Hydrochloride Suspension contains NLT 10% and NMT 20%, by weight, of ractopamine hydrochloride (C₁₈H₂₃NO₃.HCl) in water.

[Note—The material partially precipitates out at room temperature to form a slurry, and redissolves when heated to 50°–60°.]

2 IDENTIFICATION

Change to read:

Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197K (CN 1-May-2020)

Sample: Dry a portion of Ractopamine Hydrochloride Suspension under vacuum for 3 h at 60°.

3 ASSAY

Procedure

Solution A: 5.75 mg/mL solution of monobasic ammonium phosphate adjusted with 10% phosphoric acid to a pH of 4.0 ± 0.1 Solution B: 1.1 mg/mL solution of 1-heptanesulfonic acid sodium salt in Solution A

Mobile phase: Stabilizer-free tetrahydrofuran and Solution B (3:17)

Diluent: Stabilizer-free tetrahydrofuran and water (3:17). [Note—The Standard solutions and System suitability solution are stable for up to 72 h at room temperature. The Sample solution is stable for up to 90 h at room temperature.]

System suitability solution: 100 µg/mL of USP Ractopamine Hydrochloride RS and 10 µg/mL of USP Raspberry Alcohol RS in Diluent Standard solution A: 0.08 mg/mL of USP Ractopamine Hydrochloride RS in Diluent

Standard solution B: 0.1 mg/mL of USP Ractopamine Hydrochloride RS in Diluent

Standard solution C: 0.12 mg/mL of USP Ractopamine Hydrochloride RS in Diluent

Sample stock solution: Stir Ractopamine Hydrochloride Suspension in a 60° water bath for up to 1 h, to ensure complete dissolution. While hot, transfer 700 mg of the Ractopamine Hydrochloride Suspension dropwise to a 100-mL volumetric flask, and dilute with Diluent to volume.

Sample solution: Dilute a portion of the Sample stock solution with Diluent (1:10).

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 226 nm

Column: 4.6-mm × 15-cm; 5-µm packing L1

Flow rate: 1 mL/min

Injection size: 20 µL

System suitability

Samples: System suitability solution and Standard solution B

Suitability requirements

Resolution: NLT 1.5 between raspberry alcohol and ractopamine, System suitability solution

Tailing factor: NLT 0.7 and NMT 2.0 for the ractopamine peak, Standard solution B

Relative standard deviation: NMT 2.0% for three replicate injections, Standard solution B

Analysis

Samples: Standard solutions and Sample solution

Prepare a calibration curve using the three ractopamine peak responses from Standard solutions A, B, and C and their corresponding concentrations. From the graph determine the concentration, C, in mg/mL, of ractopamine hydrochloride in the Sample solution. Calculate the percentage (w/w) of C₁₈H₂₃NO₃.HCl in the portion of Ractopamine Hydrochloride Suspension taken: 1

Result = (V/W) × C_S × D × 100

V = volume of the Sample stock solution, 100 mL

W = weight of Ractopamine Hydrochloride Suspension taken (mg)

C_S = concentration of ractopamine hydrochloride from the Sample solution

D = dilution factor to prepare the Sample solution, 10

Acceptance criteria: 10%–20% of C₁₈H₂₃NO₃.HCl

4 IMPURITIES

Organic Impurities

Procedure

Solution A: 5.75 mg/mL of monobasic ammonium phosphate in water; pH NLT 4.4

Solution B: 1.1 mg/mL of 1-heptanesulfonic acid sodium salt in Solution A Solution C: Acetonitrile and Solution B (1:9)

Solution D: Acetonitrile and Solution B (17:33)

Mobile phase: See the gradient table below.

Diluent: Acetonitrile and water (1:4)

System suitability solution: 9 µg/mL each of USP Raspberry Ketone RS and USP Ractopamine Hydrochloride RS in Diluent Blank: Diluent

Sample solution A: Stir Ractopamine Hydrochloride Suspension in a 60° water bath for up to 1 h, to ensure complete dissolution. While hot, transfer 200 mg of the Ractopamine Hydrochloride Suspension dropwise into a 50-mL volumetric flask, and dilute with Diluent to volume. Sample solution B: Dilute a portion of Sample solution A with Diluent (1:100). [Note—The Sample solutions are stable for up to 48 h if stored at 5°.]

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 226 nm

Column: 4.6-mm × 25-cm; 5-µm packing L1

Flow rate: 1 mL/min

Injection size: 20 µL

System suitability

Sample: System suitability solution

Suitability requirements

Resolution: NLT 2.0 between raspberry ketone and ractopamine

Analysis

Samples: Blank, Sample solution A, and Sample solution B

[Note—Disregard any peaks that correspond to those in the Blank. Correct the response of the ractopamine peak in Sample solution B by subtracting the peak response at the retention time of ractopamine in the Blank.]

Calculate the percentage of each individual impurity in the portion of Ractopamine Hydrochloride Suspension taken:

Result = (r_A/r_B) × 100/D

r_A = peak response of each individual impurity from Sample solution A

r_B = corrected peak response for ractopamine from Sample solution B

D = dilution factor to prepare Sample solution B, 100

Acceptance criteria

Individual impurities: See Impurity Table 1.

Total impurities: NMT 3.5%

Impurity Table 1

a 4-(2-Amino-1-hydroxyethyl)phenol.

b 4-(2-Aminoethyl)phenol.

c 4-[1-Hydroxy-2-(isopropylamino)ethyl]phenol.

n d 4,4′-(Piperazine-2, 5-diyl)diphenol.

e 4-(3-Aminobutyl)phenol.

f 4-(3-Hydroxybutyl)phenol.

g 4-(4-Hydroxyphenyl)butan-2-one.

h 4-[3-(4-Hydroxyphenethylamino)butyl]phenol.

i 4-{3-[2-(4-Hydroxyphenyl)-2-methoxyethylamino]butyl}phenol.

j 4-(1-Hydroxy-2-{(4-hydroxybenzyl)[4-(4-hydroxyphenyl)butan-2-yl]amino}ethyl)phenol.

k 4-{1-Hydroxy-2-[3-(4-hydoxyphenyl)-5-methylcyclo

hexylamino]ethyl}phenol).

l 4,4′-(1,1′-Oxybis{2-[4-(4-hydroxyphenyl)butan-2-ylamino]ethane-1,1-diyl})diphenol.

5 SPECIFIC TESTS

Diastereomer Ratio

Solution A: 5.75 mg/mL of monobasic ammonium phosphate in water

Solution B: Add 10 mL of triethylamine to 950 mL of Solution A, dilute with Solution A to 1000 mL, and adjust with phosphoric acid to a pH of 4.5.

Mobile phase: Acetonitrile and Solution B (3:22)

Diluent: Acetonitrile and Solution A (1:4)

System suitability solution: 0.4 mg/mL of USP Ractopamine Hydrochloride RS in Diluent

Sample solution: Stir Ractopamine Hydrochloride Suspension in a 60° water bath for up to 1 h to ensure complete dissolution. While hot,

transfer 275 mg of it dropwise into a 100-mL volumetric flask, and dilute with Diluent to volume.

[Note—The Sample solution is stable for up to 36 h when stored at ambient conditions.]

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 226 nm

Column: 4.6-mm × 25-cm; 5-µm packing L1

Flow rate: 1 mL/min

Injection size: 20 µL

System suitability

Sample: System suitability solution

[Note—The elution order is RS,SR diastereoisomer followed by RR,SS diastereoisomer.]

Suitability requirements

Resolution: NLT 1.25 between the diastereomers

Analysis

Sample: Sample solution

Calculate the RS,SR diastereomer content, in percentage:

Result = r_A/(r_A + r_B ) × 100

r_A = peak response of the RS,SR diastereoisomer from the Sample solution

r_B = peak response of the RR,SS diastereoisomer from the Sample solution

Acceptance criteria: 45%–49%

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Store at a temperature not exceeding 70°.

Labeling: Label it to indicate that it is for veterinary use only.

USP Reference Standards 〈11〉

USP Ractopamine Hydrochloride RS

USP Raspberry Alcohol RS

4-(3-Hydroxybutyl)phenol.

C₁₀H₁₄O₂ 166.22

USP Raspberry Ketone RS

4-(4-Hydroxyphenyl)butan-2-one.

C₁₀H₁₂O₂ 164.20