Levofloxacin Tablets

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

Levofloxacin Tablets contain 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 absorption spectrum of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay. (USP 1-May-2021)

3 ASSAY

Change to read:

Procedure

Diluent: Acetonitrile and water (20:80)

Mobile phase: Transfer 874 mg of cupric sulfate, 918 mg of l-isoleucine, and 5.94 g of ammonium acetate to a suitable container. Add 700mL of water, and mix until dissolved. Add 300 mL of methanol.

Standard stock solution: 2 mg/mL of USP Levofloxacin RS in Diluent. Sonicate, if necessary, to dissolve prior to final dilution. (USP 1-May-2021)

Standard solution: 0.2 mg/mL of USP Levofloxacin RS in Mobile phase from the Standard stock solution

Sample stock solution: Nominally 5 mg/mL of levofloxacin prepared as follows. Transfer intact Tablets (NLT 5) to a volumetric flask, add 75% of the final volume of Diluent, and allow to stand for 15 min. Shake for 30 min, and dilute with Diluent to volume. Pass a portion of the solution through a suitable filter of 0.45-μm pore size, discarding the first 1–2 mL of the filtrate.

Sample solution: Nominally 0.2 mg/mL of levofloxacin in Mobile phase from the Sample stock solution

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 360 nm. For Identification B, use a diode array detector in the range of 220–400 nm. (USP 1-May-2021)

Column: 4.6-mm × 25-cm; 5-μm packing L1

Column temperature: 45°

Flow rate: 0.8 mL/min

Injection volume: 25 μL

Run time: 2 times the retention time of levofloxacin

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 1.8

Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of levofloxacin (C₁₈H₂₀FN₃O₄) in the portion of Tablets taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response of levofloxacin 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)

Acceptance criteria: 90.0%–110.0%

4 PERFORMANCE TESTS

Dissolution 〈711〉

Test 1

Medium: 0.1 N hydrochloric acid; 900 mL

Apparatus 2: 75 rpm

Time: 30 min

Standard solution: 0.56 mg/mL of USP Levofloxacin RS in Medium

Sample solution: Pass a portion of the solution under test through a suitable filter of 0.45-μm pore size.

Instrumental conditions

(See Ultraviolet-Visible Spectroscopy 〈857〉.)

Mode: UV

Analytical wavelength: 294 nm

Cell length: 0.1 mm

Blank: Medium

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage (Q) of the labeled amount of levofloxacin (C₁₈H₂₀FN₃O₄) dissolved:

Result = (A_U/A_S) × C_S × V × D × (1/L) × 100

A_U = absorbance of the Sample solution

A_S = absorbance of the Standard solution

C_S = concentration of the Standard solution (mg/mL)

V = volume of Medium, 900 mL

D = dilution factor of the Sample solution

L = label claim (mg/Tablet)

Tolerances: NLT 80% (Q) of the labeled amount of levofloxacin (C₁₈H₂₀FN₃O₄) is dissolved.

Test 2

Medium: 0.1 N hydrochloric acid; 900 mL

Apparatus 1: 100 rpm

Time: 30 min

Standard solution: L/900 mg/mL of USP Levofloxacin RS in Medium. Mix to obtain solutions with known concentrations as indicated in Table 1, where L is the label claim in mg/Tablet.

Sample solution: Pass a portion of the solution under test having a concentration similar to that of the Standard solution through a suitable filter of 0.45-μm pore size.

Table 1

Instrumental conditions

(See Ultraviolet-Visible Spectroscopy 〈857〉.)

Mode: UV

Analytical wavelength: 293 nm

Cell length: 0.1 mm

Blank: Medium

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage (Q) of the labeled amount of levofloxacin (C₁₈H₂₀FN₃O₄) dissolved:

Result = (A_U/A_S) × C_S × V × D × (1/L) × 100

A_U = absorbance of the Sample solution

A_S = absorbance of the Standard solution

C_S = concentration of the Standard solution (mg/mL)

V = volume of Medium, 900 mL

D = dilution factor of the Sample solution

L = label claim (mg/Tablet)

Tolerances: NLT 80% (Q) of the labeled amount of levofloxacin (C₁₈H₂₀FN₃O₄) is dissolved.

Test 3

Medium: 0.1 N hydrochloric acid; 900 mL

Apparatus 1: 100 rpm

Time: 30 min

Standard solution: L/900 mg/mL of USP Levofloxacin RS in Medium. Mix to obtain solutions with known concentrations as indicated in Table 1, where L is the label claim in mg/Tablet.

Sample solution: Pass a portion of the solution under test having the same concentration as that of the Standard solution through a suitable filter of 0.45-μm pore size.

Instrumental conditions

(See Ultraviolet-Visible Spectroscopy 〈857〉.)

Mode: UV

Analytical wavelength: 326 nm

Cell length: 1 mm for a 250-mg Tablet, 0.5 mm for a 500-mg Tablet, and 0.2 mm for a 750-mg Tablet

Blank: Medium

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage (Q) of the labeled amount of levofloxacin (C₁₈H₂₀FN₃O₄) dissolved:

Result = (A_U/A_S) × C_S × V × D × (1/L) × 100

A_U = absorbance of the Sample solution

A_S = absorbance of the Standard solution

C_S = concentration of the Standard solution (mg/mL)

V = volume of Medium, 900 mL

D = dilution factor of the Sample solution

L = label claim (mg/Tablet)

Tolerances: NLT 80% (Q) of the labeled amount of levofloxacin (C₁₈H₂₀FN₃O₄) is dissolved.

Test 4

Medium: 0.1 N hydrochloric acid; 900 mL

Apparatus 1: 100 rpm

Time: 30 min

Standard solution: 16 μg/mL of USP Levofloxacin RS in Medium

Sample solution: Pass a portion of the solution under test having the same concentration as that of the Standard solution through a suitable filter of 0.45-μm pore size.

Instrumental conditions

(See Ultraviolet-Visible Spectroscopy 〈857〉.)

Mode: UV

Analytical wavelength: 332 nm

Cell length: 1 cm

Blank: Medium

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage (Q) of the labeled amount of levofloxacin (C₁₈H₂₀FN₃O₄) dissolved:

Result = (A_U/A_S) × C_S × V × D × (1/L) × 100

A_U = absorbance of the Sample solution

A_S = absorbance of the Standard solution

C_S = concentration of the Standard solution (mg/mL)

V = volume of Medium, 900 mL

D = dilution factor of the Sample solution

L = label claim (mg/Tablet)

Tolerances: NLT 80% (Q) of the labeled amount of levofloxacin (C₁₈H₂₀FN₃O₄) is dissolved.

Uniformity of Dosage Units 〈905〉: Meet the requirements

5 IMPURITIES

Change to read:

Organic Impurities

Diluent, Mobile phase, Standard stock solution, Sample solution, and Chromatographic system: Proceed as directed in the Assay.

Standard solution A: 0.2 mg/mL of USP Levofloxacin RS in Mobile phase from the Standard stock solution

Standard solution B: 0.001 mg/mL of USP Levofloxacin Related Compound A RS in Mobile phase (USP 1-May-2021)

System suitability

Sample: Standard solution A (USP 1-May-2021)

Suitability requirements

Tailing factor: NMT 1.8 (USP 1-May-2021)

Relative standard deviation: NMT 2.0% (USP 1-May-2021)

Analysis

Samples: Sample solution, Standard solution A, and Standard solution B (USP 1-May-2021)

Calculate the percentage of levofloxacin related compound A in the portion of Tablets taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response of levofloxacin related compound A from the Sample solution

r_S = peak response of levofloxacin related compound A from Standard solution B (USP 1-May-2021)

C_S = concentration of USP Levofloxacin Related Compound A RS in Standard solution B (USP 1-May-2021) (mg/mL)

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

Calculate the percentage of any other impurities in the portion of Tablets taken:

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

r_U = peak response of any impurity from the Sample solution

r_S = peak response of levofloxacin from Standard solution A (USP 1-May-2021)

C_S = concentration of USP Levofloxacin RS in Standard solution A (USP 1-May-2021) (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.

Table 2

^a (S)-9-Fluoro-2,3-dihydro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-7H-pyrido[1,2,3-de][1,4]benzoxazine.

^b (S)-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.

^c (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.

^d (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.

^e (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.

^f Process impurity, for information only.

^g (R)-9-Fluoro-2,3-dihydro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-7H-pyrido[1,2,3-de][1,4]benzoxazine-6-carboxylic acid.

^h (S)-10-fluoro-3-methyl-9-(4-methylpiperazin-1-yl)-7-oxo-3,7-dihydro-7H-pyrido[1,2,3-de][1,4]benzoxazine-6-carboxylic acid.

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight containers. Store at controlled room temperature.

Labeling: When more than one Dissolution test is given, the labeling states the Dissolution test used only if Test 1 is not used.

USP Reference Standards 〈11〉

USP Levofloxacin RS

USP Levofloxacin Related Compound A RS(S)-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.

C₁₇H₁₈FN₃O₄ 347.34