Vancomycin 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 Injection is a sterile solution of Vancomycin or Vancomycin Hydrochloride in Water for Injection. It contains NLT 90.0% and NMT 115.0% of the labeled amount of vancomycin (C₆₆H₇₅Cl₂N₉O₂₄). It contains one or more suitable excipients.

2 IDENTIFICATION

A. The retention time of the main vancomycin peak of the Sample stock solution, obtained as directed in Composition of Vancomycin, corresponds to that of a similarly prepared solution of USP Vancomycin Hydrochloride RS.

3 ASSAY

3.1 Antibiotics-Microbial Assays 〈81〉

Sample solution: Allow a container of Injection to thaw, if applicable, and mix the solution. Dilute a portion of this solution with Buffer B.4 to yield a test dilution having a concentration assumed to be equal to that of the median dose of the standard.

Analysis: Proceed as directed for vancomycin in the chapter.

Acceptance criteria: 90.0%–115.0%

4 SPECIFIC TESTS

Change to read:

4.1 Composition of Vancomycin

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

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

Solution B: Acetonitrile, tetrahydrofuran, and Buffer (29:1:70)

Mobile phase: See Table 1. Make adjustments if necessary, changing the acetonitrile proportion in Solution A to obtain a retention time of 7.5–10.5 min for the main vancomycin peak.

Table 1

System suitability solution: Allow a container of Injection to thaw, if applicable, and mix the solution. Dilute a portion of the Injection with water to obtain a solution containing 0.5 mg/mL of vancomycin. Heat at 65° for 24 h, and allow to cool.

Sample stock solution: Allow a container of Injection to thaw, if applicable, and mix the solution.

Sample solution: Equivalent to 0.4 mg/mL of vancomycin or vancomycin hydrochloride from the Sample stock solution in Solution A

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
• Suitability requirements
• [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 B is increasing from 0% to 100%.]
• Resolution: NLT 3.0 between compound 1 and vancomycin B
• Column efficiency: NLT 1500 theoretical plates for the vancomycin B peak

Analysis

Samples: Sample stock solution and Sample solution

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.

Correct any peak observed in the chromatograms from Sample stock solution and Sample solution by subtracting the area response of any peak observed in the chromatogram of Solution A at the corresponding retention time.

Calculate the percentage of vancomycin B in the portion of Injection taken:

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

D = dilution factor, Sample stock solution to Sample solution

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

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

Calculate the percentage of any individual peak, other than the main peak, in the portion of Injection taken:

Result = {rᵢ/[(D × r_B) + r_A]} × 100

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

D = dilution factor, Sample stock solution to Sample solution

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

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

Acceptance criteria: NLT 88% of vancomycin B; NMT 4% of any individual peak other than the main peak

Change to read:

pH 〈791〉: For products formulated with vancomycin hydrochloride, 4.5–5.5 for products stored at room temperature; 3.0–5.0 for products maintained in a frozen state; 3.9–4.3 for products formulated with vancomycin and stored at room temperature

Bacterial Endotoxins Test 〈85〉: NMT 0.33 USP Endotoxin Units/mg of vancomycin

Particulate Matter in Injections 〈788〉: Meets the requirements for small-volume injections or large-volume injections, whichever is applicable

Sterility Tests 〈71〉, Test for Sterility of the Product to Be Examined, Membrane Filtration: Meets the requirements, except use water instead of diluting Fluid A

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

5 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve as described in Packaging and Storage Requirements 〈659〉, Injection Packaging. Store as directed by product label.

Change to read:

Labeling: It meets the requirements in Labeling 〈7〉, Labels and Labeling for Injectable Products. For the product stored in a frozen state, the label states that it is to be thawed just before use, describes conditions for proper storage of the resultant solution, and directs that the solution is not to be refrozen. The label states whether the product contains Vancomycin or Vancomycin Hydrochloride.

USP Reference Standards 〈11〉

USP Vancomycin Hydrochloride RS