Terbutaline Sulfate

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

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

DOWNLOAD PDF HERE

1 DEFINITION

Terbutaline Sulfate contains NLT 98.0% and NMT 102.0% (USP 1-Dec-2023) of terbutaline sulfate [(C₁₂H₁₉NO₃)₂ · H₂SO₄], calculated on the dried basis.

2 IDENTIFICATION

Change to read:

A. SPECTROSCOPIC IDENTIFICATION TESTS 〈197〉 , Infrared Spectroscopy: 197K or 197A (USP 1-Dec-2023)

B. The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay. Add the following:

C. IDENTIFICATION TESTS—GENERAL 〈191〉 , Chemical Identification Tests, Sulfate: Meets the requirements (USP 1-Dec-2023)

3 ASSAY

Change to read:

PROCEDURE

Buffer: 3.15 g/L of ammonium formate and 5.49 g/L of sodium 1-hexanesulfonate in water prepared as follows. Transfer 3.15 g of ammonium formate to a 1000-mL volumetric flask, dissolve in 900 mL of water, adjust the solution with formic acid to a pH of 3.0, add 5.49 g of sodium 1-hexanesulfonate, and dilute with water to volume.

Mobile phase: Methanol and Buffer (23:77)

System suitability solution: 1.0 mg/mL of USP Terbutaline Sulfate RS and 0.4 mg/mL of USP Terbutaline Related Compound A RS in Mobile phase

Standard solution: 1.0 mg/mL of USP Terbutaline Sulfate RS in Mobile phase Sample solution: 1.0 mg/mL of Terbutaline Sulfate in Mobile phase Chromatographic system

(See Chromatography 〈621〉, System Suitability.) Mode: LC

Detector: UV 276 nm

Column: 4.6-mm × 15-cm; 5-µm packing L1 Flow rate: 1 mL/min

Injection volume: 20 µL

Run time: NLT 1.6 times the retention time of terbutaline (USP 1-Dec-2023)

System suitability

Sample: System suitability solution

[NOTE—The relative retention times for terbutaline related compound A and terbutaline are 0.9 and 1.0, respectively.] Suitability requirements

Resolution: NLT 2.0 between terbutaline related compound A and terbutaline

(USP 1-Dec-2023)

Tailing factor: NMT 2.0 for terbutaline

Relative standard deviation: NMT 0.73% (USP 1-Dec-2023) for terbutaline Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of terbutaline sulfate [(C₁₂H₁₉NO₃)₂ · H₂SO₄] in the portion of Terbutaline Sulfate taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response of terbutaline from the Sample solution

r_S = peak response of terbutaline from the Standard solution

C_S = concentration of USP Terbutaline Sulfate RS in the Standard solution (mg/mL)

C_U = concentration of Terbutaline Sulfate in the Sample solution (mg/mL)

Acceptance criteria: 98.0%–102.0% (USP 1-Dec-2023) on the dried basis

4 IMPURITIES

RESIDUE ON IGNITION 〈281〉: NMT 0.2%

Change to read:

ORGANIC IMPURITIES

Buffer and System suitability solution: Prepare as directed in the Assay.

Solution A: Methanol and Buffer (23:77)

Solution B: Methanol

Mobile phase: See Table 1.

Table 1

Sensitivity solution: 0.75 µg/mL of USP Terbutaline Sulfate RS in Solution A

Standard solution: 0.003 mg/mL each of USP Terbutaline Sulfate RS, USP Terbutaline Related Compound A RS, and USP Terbutaline Related Compound D RS in Solution A

Sample solution: 1.5 mg/mL of Terbutaline Sulfate in Solution A

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 276 nm

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

Flow rate: 1 mL/min

Injection volume: 20 µL

System suitability

Samples: System suitability solution, Sensitivity solution, and Standard solution [NOTE—See Table 2 for the relative retention times.]

Suitability requirements

Resolution: NLT 2.0 between terbutaline related compound A and terbutaline, System suitability solution Tailing factor: NMT 2.0 for terbutaline, System suitability solution

Relative standard deviation: NMT 5.0% for terbutaline, terbutaline related compound A, and terbutaline related compound D, Standard solution

Signal-to-noise ratio: NLT 10, Sensitivity solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of terbutaline related compound A in the portion of Terbutaline Sulfate taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response of terbutaline related compound A from the Sample solution

r_S = peak response of terbutaline related compound A from the Standard solution

C_S = concentration of USP Terbutaline Related Compound A RS in the Standard solution (mg/mL)

C_U = concentration of Terbutaline Sulfate in the Sample solution (mg/mL)

Calculate the percentage of terbutaline related compound D in the portion of Terbutaline Sulfate taken:

Result = (r_U/r_S) × (C_S/C_U) × (M_r1/M_r2) × 100

r_U = peak response of terbutaline related compound D from the Sample solution

r_S = peak response of terbutaline related compound D from the Standard solution

C_S = concentration of USP Terbutaline Related Compound D RS in the Standard solution (mg/mL)

C_U = concentration of Terbutaline Sulfate in the Sample solution (mg/mL)

M_r1 = molecular weight of terbutaline related compound D sulfate salt (2:1), 724.87

M_r2 = molecular weight of terbutaline related compound D free base times 2, 626.80

Calculate the percentage of any unspecified impurity in the portion of Terbutaline Sulfate taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response of any unspecified impurity from the Sample solution

r_S = peak response of terbutaline from the Standard solution

C_S = concentration of USP Terbutaline Sulfate RS in the Standard solution (mg/mL)

C_U = concentration of Terbutaline Sulfate in the Sample solution (mg/mL)

Acceptance criteria: See Table 2. The reporting threshold is 0.05%.

Table 2

^a  Excluding terbutaline related compound A.

(USP 1-Dec-2023)

5 SPECIFIC TESTS

Change to read:

5.1 ACIDITY

Sample solution: 20 mg/mL in carbon dioxide-free water

Analysis: Titrate 10 mL of the Sample solution with 0.02 N sodium hy droxide VS (USP 1-Dec-2023) from a microburet to a pH of 6, determining the endpoint potentiometrically, using a calomel-glass electrode system.

Acceptance criteria: NMT 0.50 mL of 0.02 N sodium hydroxide VS (USP 1-Dec-2023) is required (0.3% as acetic acid).

5.2 LOSS ON DRYING 〈731〉

Analysis: Dry at 105° for 3 h.

Acceptance criteria: NMT 0.5%

6 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in well-closed, light-resistant containers. Store at controlled room temperature.

Change to read:

USP REFERENCE STANDARDS 〈11〉

USP Terbutaline Sulfate RS

USP Terbutaline Related Compound A RS

2-(tert-Butylamino)-1-(3,5-dihydroxyphenyl)ethan-1-one  sulfate.           (C₁₂H₁₉NO₃)₂ · H₂SO₄           544.62

USP Terbutaline Related Compound D RS

2-[Benzyl(tert-butyl)amino]-1-(3,5-dihydroxyphenyl)ethan-1-one.          C₁₉H₂₃NO₃             313.40 (USP 1-Dec-2023)