Levofloxacin Oral Solution

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

Levofloxacin Oral Solution contains NLT 90.0% and NMT 110.0% of the labeled amount of levofloxacin (C₁₈H₂₀FN₃O₄).

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.

Add the following:

B. 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-May-2024)

3 ASSAY

Change to read:

Procedure

[Note—Protect the solutions of levofloxacin from light.]

Diluent: Acetonitrile and water (18:82)

Mobile phase: Add 1 mL of trifluoroacetic acid to each 1000 mL of Diluent

System suitability solution: 0.1025 mg/mL each of USP Levofloxacin RS and USP Levofloxacin Related Compound A RS in Diluent

Standard solution: 0.1025 mg/mL of USP Levofloxacin RS in Diluent

Sample solution: Nominally (USP 1-May-2024) 0.1025 mg/mL of levofloxacin prepared in Diluent based on the label claim. [Note—Mix the solution well after equilibrating the solution for 4 h at room temperature while protected from light.]

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 294 nm. For Identification B, use a diode array detector in the range of 200–400 nm. (USP 1-May-2024)

Column: 4.6-mm × 15-cm; 3.5-μm packing L11

Column temperature: 30°

Flow rate: 0.7 mL/min

Injection volume: 20 μL

Run time: NLT (USP 1-May-2024) 2.5 times the retention time of levofloxacin

System suitability

Samples: System suitability solution and Standard solution

Suitability requirements

Resolution: NLT 1.9 between levofloxacin related compound A and levofloxacin, System suitability solution

Tailing factor: NMT 2.0, Standard solution (USP 1-May-2024)

Relative standard deviation: NMT 1.0% (USP 1-May-2024) , Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of levofloxacin (CC₁₈H₂₀FN₃O₄) in the portion of Oral Solution taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response of levofloxacin (USP 1-May-2024) from the Sample solution

r_S = peak response of levofloxacin (USP 1-May-2024) from the Standard solution

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

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

Acceptance criteria: 90.0%–110.0%

4 IMPURITIES

Change to read:

Organic Impurities

[Note—Protect the solutions of levofloxacin from light.]

Diluent, Mobile phase, (USP 1-May-2024) System suitability solution, Sample solution, and Chromatographic system (USP 1-May-2024): Proceed as directed in the Assay.

Standard solution: 0.000205 mg/mL of USP Levofloxacin RS in Diluent

Sensitivity solution: 0.1025 μg/mL of USP Levofloxacin RS from the Standard solution in Diluent

System suitability

Samples: System suitability solution, Standard solution, and Sensitivity solution

[Note—The relative retention times in Table 1 are provided as information that could aid in peak assignment.]

Table 1

^a (S)-2,3-Dihydro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-7H-pyrido[1,2,3-de][1,4]benzoxazine-6-carboxylic acid.

^b (S)-9-Fluoro-2,3-dihydro-3-methyl-10-[2-(methylamino)ethylamino]-7-oxo-7H-pyrido[1,2,3-de][1,4]benzoxazine-6-carboxylic acid.

^c (S)-4-(6-Carboxy-9-fluoro-2,3-dihydro-3-methyl-7-oxo-7H-pyrido-[1,2,3-de][1,4]benzoxazine-10-yl)-1-methylpiperazine 1-oxide.

Suitability requirements

Resolution: NLT 1.9 between levofloxacin related compound A and levofloxacin, System suitability solution

Relative standard deviation: NMT 5.0%, Standard solution

Signal-to-noise ratio: NLT 10, Sensitivity solution (USP 1-May-2024)

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of each degradation product (USP 1-May-2024) in the portion of Oral Solution taken:

Result = (r_U/r_S) × (C_S/C_U) × (1/F) × 100

r_U = peak response of each degradation product (USP 1-May-2024) from the Sample solution

r_S = peak response of levofloxacin from the Standard solution

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

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

F = relative response factor (see Table 2)

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

Table 2

(USP 1-May-2024)

5 SPECIFIC TESTS

Microbial Enumeration Tests 〈61〉 and Tests For Specified Microorganisms 〈62〉: The total aerobic microbial count does not exceed 102 cfu/mL, and the total combined molds and yeast count does not exceed 101 cfu/mL. It also meets the requirement for absence of Escherichia coli.

Deliverable Volume 〈698〉: Meets the requirements

pH 〈791〉: 5.0–6.0

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Protect from light. Store at controlled room temperature.

Change to read:

USP Reference Standards 〈11〉

USP Levofloxacin RS

(USP 1-May-2024)

USP Levofloxacin Related Compound A RSS)-9-Fluoro-3-methyl-10-(piperazin-1-yl)-7-oxo-2,3-dihydro-7H-pyrido[1,2,3-de][1,4]benzoxazine-6-carboxylic acid. (USP 1-May-2024)

C₁₇H₁₈FN₃O₄ 347.35 (USP 1-May-2024)