Terbutaline Sulfate Injection

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 Injection is a sterile solution of Terbutaline Sulfate in Water for Injection. It contains NLT 90.0% and NMT 110.0% of the labeled amount of terbutaline sulfate [(C₁₂H₁₉NO₃)₂ · H₂SO₄].

[CAUTION—Do not use the Injection if it is discolored.]

2 IDENTIFICATION

Delete the following:

A. THIN LAYER CHROMATOGRAPHY (USP 1-DEC-2023)

Add the following:

A. The UV spectrum of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay. (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.

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: Nominally 1.0 mg/mL from a volume of Injection. If necessary, dilute with water.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 276 nm. For Identification A, use a diode array detector in the range of 240–400 nm. (USP 1-Dec-2023)

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 1.0% (USP 1-Dec-2023) for terbutaline

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of terbutaline sulfate [(C₁₂H₁₉NO₃)₂ · H₂SO₄] in the portion of Injection 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 = nominal concentration of terbutaline sulfate in the Sample solution (mg/mL)

Acceptance criteria: 90.0%–110.0% Add the following:

4 IMPURITIES

4.1 ORGANIC IMPURITIES

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.

Solution A: Methanol and Buffer (23:77)

Solution B: Methanol

Mobile phase: See Table 1.

Table 1

System suitability solution: 0.2 mg/mL of USP Terbutaline Sulfate RS and 0.08 mg/mL of USP Terbutaline Related Compound A RS in Solution A

Sensitivity solution: 0.0003 mg/mL of USP Terbutaline Sulfate RS in Solution A

Standard solution: 0.0006 mg/mL each of USP Terbutaline Sulfate RS and USP Terbutaline Related Compound A RS in Solution A Sample solution: Nominally 0.3 mg/mL of terbutaline sulfate, from the pooled content of Injection from vials (NLT 5), 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: 100 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 1.5 between terbutaline related compound A and terbutaline, System suitability solution Relative standard deviation: NMT 5.0% from terbutaline and terbutaline related compound A, 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 Injection 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 = nominal concentration of terbutaline sulfate in the Sample solution (mg/mL)

Calculate the percentage of any unspecified degradation product in the portion of Injection taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response of any unspecified degradation product 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 = nominal concentration of terbutaline sulfate in the Sample solution (mg/mL)

Acceptance criteria: See Table 2. The reporting threshold is 0.1%.

Table 2

5 SPECIFIC TESTS

Change to read:

BACTERIAL ENDOTOXINS TEST 〈85〉: Meets the requirements (USP 1-Dec-2023)

Add the following:

STERILITY TESTS 〈71〉: Meets the requirements (USP 1-Dec-2023)

PH 〈791〉: 3.0–5.0

OTHER REQUIREMENTS: It meets the requirements under Injections and Implanted Drug Products 〈1〉.

6 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in single-dose containers, preferably of Type I glass, protected from light. 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.  (C₁₂H₁₇NO₃)₂ · H₂SO₄          544.62 (USP 1-Dec-2023)