Dobutamine in Dextrose 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

Dobutamine in Dextrose Injection is a sterile solution of Dobutamine Hydrochloride and Dextrose in Water for Injection. It contains an amount of Dobutamine Hydrochloride equivalent to NLT 90.0% and NMT 110.0% of the labeled amount of dobutamine (C₁₈H₂₃NO₃) and NLT 90.0% and NMT 110.0% of the labeled amount of dextrose (C₆H₁₂O₆· H₂O). It may contain one or more suitable antioxidants or chelating agents.

2 IDENTIFICATION

A. The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay,

Procedure 2: Dobutamine.

B.

Sample solution: Nominally 50 mg/mL of dextrose from Injection

Analysis: Add a few drops of the Sample solution to 5 mL of hot alkaline cupric tartrate TS.

Acceptance criteria: A copious red precipitate of cuprous oxide is formed.

3 ASSAY

Change to read:

Procedure 1: Dextrose

Sample solution: Injection

Analysis

Sample: Sample solution

Determine the angular rotation of the Sample solution in a suitable polarimeter tube (see Optical Rotation 〈781〉).

Calculate the percentage of the labeled amount of dextrose (C₆H₁₂O₆· H₂O) in the portion of Injection taken:

Result = [(100 × a)/ _{(ERR 1-Jan-2021)} (l × _{(ERR 1-Jan-2021)} α)] × (1/C_U) × (M_r1/M_r2) × 100

a = observed rotation (°)

l = length of the polarimeter tube (dm)

α = midpoint of the speci

c rotation range for anhydrous dextrose, 52.9°

C_U= nominal concentration of dextrose in the Sample solution (g/100 mL)

M_r1= molecular weight of dextrose monohydrate, 198.17

M_r2= molecular weight of anhydrous dextrose, 180.16

Acceptance criteria: 90.0%–110.0%

Procedure 2: Dobutamine

Buffer: Transfer about 23 g of monobasic ammonium phosphate to a 2-L volumetric flask. Add 1900 mL of water. Adjust with phosphoric acid to a pH of 2.2, and dilute with water to volume.

Mobile phase: Acetonitrile and Buffer (20:80). Filter and degas.

System suitability solution: 0.5 mg/mL of USP Dobutamine Hydrochloride RS and 0.01 mg/mL of 5-hydroxymethylfurfural in water

Standard solution: 0.5 mg/mL of USP Dobutamine Hydrochloride RS in water. [Note—Prepare fresh daily, and refrigerate until injected.]

Sample solution: Nominally 0.446 mg/mL of dobutamine from Injection in water. [Note—Refrigerate until injected, and use within 8 h.]

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 280 nm

Column: 3.9-mm × 30-cm; packing L1

Flow rate: 1.5 mL/min

Injection volume: 20 μL

System suitability

Samples: System suitability solution and Standard solution

Suitability requirements

Relative retention time: 1.0 for dobutamine and NMT 0.62 for 5-hydroxymethylfurfural, System suitability solution

Retention time: NMT 5.3 min for dobutamine, System suitability solution

Tailing factor: NMT 2.0, Standard solution

Relative standard deviation: NMT 2.0%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of dobutamine (C₁₈H₂₃NO₃) in the portion of Injection taken:

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

r_U= peak response of dobutamine from the Sample solution

r_S= peak response of dobutamine from the Standard solution

C_S= concentration of USP Dobutamine Hydrochloride RS in the Standard solution (mg/mL)

C_U= nominal concentration of dobutamine in the Sample solution (mg/mL)

M_r1= molecular weight of dobutamine, 301.39

M_r2= molecular weight of dobutamine hydrochloride, 337.84

Acceptance criteria: 90.0%–110.0%

4 IMPURITIES

Organic Impurities

Buffer, Mobile phase, System suitability solution, Standard solution, and Chromatographic system: Proceed as directed in the Assay,

Procedure 2: Dobutamine.

Sample solution: Nominally 0.446 mg/mL of dobutamine from Injection in water

Analysis

Sample: Sample solution

Calculate the percentage of each impurity, excluding 5-hydroxymethylfurfural from all calculations, in the portion of Injection taken:

Result = (r_U/r_T) × 100

r_U= peak response for each impurity

r_T= sum of all the peak responses

Acceptance criteria

Any individual impurity: NMT 1.0%

Total impurities: NMT 2.0%

Limit of 5-Hydroxymethylfurfural

Ion-exchange column: Fill an 8-mm chromatographic tube to a height of 40 mm with a 100- to 200-mesh, strongly acidic, styrene-divinylbenzene cation-exchange resin. Wash the column with 30 mL of water, and discard the eluate.

[Note—Prepare a new column for each Sample solution and Blank, and use each column only once.]

Sample solution: Transfer 2 mL of Injection to the Ion-exchange column, and collect the eluate in a 50-mL volumetric flask. Pass 25 mL of water through the column, and collect the eluate in the same volumetric flask. Dilute the eluate with water to volume. Remove the stopper from the flask, and allow the solution to stand for about 30 min in order to oxidize any bisulfite ions present.

Blank: Prepare as directed in the Sample solution by passing 27 mL of water through an Ion-exchange column and collecting the eluate in a 50-mL volumetric flask. Dilute with water to volume.

Instrumental conditions

Mode: UV

Analytical wavelength: 284 nm

Cell: 1 cm

Analysis

Samples: Sample solution and Blank

Determine the absorbance of the Sample solution after correcting for the Blank.

Acceptance criteria: NMT 0.25

5 SPECIFIC TESTS

pH 〈791〉: 2.5–5.5

Particulate Matter in Injections 〈788〉: Meets the requirements for large-volume injections

Bacterial Endotoxins Test 〈85〉: NMT 5.56 USP Endotoxin Units/mg of dobutamine

Other Requirements: Meets the requirements in Injections and Implanted Drug Products 〈1〉

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in single-dose containers, preferably of Type II glass, or of a suitable plastic material. Store at room temperature, avoid excessive heat, and protect from freezing.

Labeling: The label states the total osmolar concentration in mOsmol/L.

USP Reference Standards 〈11〉

USP Dobutamine Hydrochloride RS