Vancomycin Hydrochloride for Injection

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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1 DEFINITION

Vancomycin Hydrochloride for Injection is a sterile dry mixture of Vancomycin Hydrochloride and may contain a suitable stabilizing agent. It contains NLT 90.0% and NMT 115.0% of the labeled amount of vancomycin.

2 IDENTIFICATION

Change to read:

Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197K

3 ASSAY

3.1 Antibiotics-Microbial Assays 〈81〉

Sample solution 1 (where it is represented as being in a single-dose container): Constitute a container of Vancomycin Hydrochloride for Injection in water corresponding to the volume of diluent specified in the labeling. Withdraw all of the withdrawable contents, using a suitable hypodermic needle and syringe. Dilute to an equivalent of 1 mg/mL of vancomycin with water.

Sample solution 2 (where it is packaged for dispensing): Dissolve the contents of 1 container of Vancomycin Hydrochloride for Injection in water, and dilute with water to obtain a solution having a concentration of 1 mg/mL of vancomycin.

Sample solution 3 (where the label states the quantity of vancomycin in a given volume of constituted solution): Constitute a container of Vancomycin Hydrochloride for Injection in water corresponding to the volume of diluent specified in the labeling. Dilute a portion to obtain a final concentration equivalent to 1 mg/mL of vancomycin in water.

Analysis: Proceed as directed in Antibiotics-Microbial Assays 〈81〉. [Note-Use a measured volume of the appropriate Sample solution, diluted quantitatively with Buffer B.4 to yield a Test Dilution having a concentration assumed to be equal to the median dose level of the Standard.]

Acceptance criteria: 90.0%–115.0%

4 PERFORMANCE TESTS

Uniformity of Dosage Units 〈905〉: Meets the requirements

5 SPECIFIC TESTS

5.1 Particulate Matter in Injections 〈788〉

Meets the requirements under small-volume injections

5.2 Bacterial Endotoxins Test 〈85〉

NMT 0.33 USP Endotoxin Unit/mg of vancomycin

5.3 Sterility Tests 〈71〉

It meets the requirements when tested as directed for Test for Sterility of the Product to Be Examined, Membrane Filtration, except to dissolve the specimen in water instead of in Fluid A.

5.4 pH 〈791〉

2.5–4.5, 50 mg/mL in water

5.5 Water Determination, Method I 〈921〉

NMT 5.0%

5.6 Injections and Implanted Drug Products 〈1〉, Specific Tests, Completeness and clarity of solutions

Meets the requirements at the time of use.

5.7 Content of Vancomycin

Solution A: Triethylamine and water (1:500). Adjust with phosphoric acid to a pH of 3.2.

Solution B: Acetonitrile, tetrahydrofuran, and Solution A (7:1:92)

Solution C: Acetonitrile, tetrahydrofuran, and Solution A (29:1:70)

Mobile phase: See the gradient table below.

[Note-Make adjustments if necessary, changing the acetonitrile proportion in Solution B to obtain a retention time of 7.5–10.5 min for the main vancomycin peak.]

System suitability solution: 0.5 mg/mL of USP Vancomycin Hydrochloride RS. Heat at 65° for 48 h, and allow to cool.

Sample solution 1: Equivalent to 10 mg/mL of vancomycin from Vancomycin Hydrochloride for Injection in Solution B

Sample solution 2: 0.4 mg/mL of vancomycin from Sample solution 1 in Solution B

Chromatographic system

• (See Chromatography 〈621〉, System Suitability.)
• Mode: LC
• Detector: UV 280 nm
• Column: 4.6-mm × 25-cm; 5-µm packing L1
• Flow rate: 2 mL/min
• Injection size: 20 µL

System suitability

• Sample: System suitability solution
• [Note-The elution order is compound 1, vancomycin B, and compound 2. Compound 2 elutes 3–6 min after the start of the period when the percentage of Solution C increases from 0% to 100%.]
• Suitability requirements
• Resolution: NLT 3.0 between compound 1 and vancomycin B
• Column efficiency: NLT 1500 theoretical plates, calculated from the vancomycin B peak

Analysis

Samples: Sample solution 1 and Sample solution 2

[Note-Where baseline separation is not achieved, peak areas are defined by vertical lines extended from the valleys between peaks to the baseline. The main component peak may include a fronting shoulder, which is attributed to monodechlorovancomycin. This shoulder should not be integrated separately.]

[Note-Correct any peak observed in the chromatograms obtained from Sample solution 1 and Sample solution 2 by subtracting the area response of any peak observed in the chromatogram of Solution B at the corresponding elution time.]

Measure the area responses for all of the peaks.

Calculate the percentage of vancomycin B in the specimen tested:

Result = [D × r_ᴮ /((D × r_ᴮ) + r_ᴬ)] × 100

D = dilution factor, Sample solution 1 to Sample solution 2, 25

r_ᴮ = corrected area response of the main peak from Sample solution 2

r_ᴬ = sum of the corrected area responses of all the peaks, other than the main peak, from Sample solution 1

Calculate the percentage of each other peak taken:

Result = {rᵢ /[(D × r_ᴮ) + r_ᴬ]} × 100

rᵢ = corrected area response of any individual peak, other than the main peak, from Sample solution 1

D = dilution factor, Sample solution 1 to Sample solution 2, 25

Acceptance criteria: NLT 80.0% of vancomycin B; NMT 9.0% of any peak other than the main peak

5.8 Other Requirements

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

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve as described in Packaging and Storage Requirements 〈659〉, Injection Packaging, Packaging for constitution.

Labeling: Meets the requirements under Labeling 〈7〉, Labels and Labeling for Injectable Products

USP Reference Standards 〈11〉

USP Vancomycin Hydrochloride RS