Gemifloxacin Mesylate

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

C₁₈H₂₀FN₅O₄·CH₄O₃S 485.49

(Z)-7-[3-(Aminomethyl)-4-(methoxyimino)-1-pyrrolidinyl]-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acid monomethanesulfonate;

(±)-7-[3-(Aminomethyl)-4-oxo-1-pyrrolidinyl]-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acid, 7⁴-(Z)-(O-methyloxime), monomethanesulfonate;

(Z)-7-[3-(Aminomethyl)-4-(methoxyimino)pyrrolidin-1-yl]-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid methanesulfonate CAS RN^®: 210353-53-0.

1 DEFINITION

Gemifloxacin Mesylate contains NLT 98.0% and NMT 102.0% of gemifloxacin mesylate (C₁₈H₂₀FN₅O₄·CH₄O₃S), calculated on the anhydrous and solvent-free basis.

2 IDENTIFICATION

A. SPECTROSCOPIC IDENTIFICATION TESTS (197), Infrared Spectroscopy: 197K or 197M

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

3 ASSAY

3.1 PROCEDURE

Store the solutions in amber vials and protect from light.

Mobile phase: Acetonitrile, water, and trifluoroacetic acid (20: 80:0.1)

Standard solution: 0.5 mg/mL of USP Gemifloxacin Mesylate RS in water

Sample solution: 0.5 mg/mL of Gemifloxacin Mesylate in water

3.2 Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 272 nm

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

Column temperature: 40°

Flow rate: 1 mL/min

Injection volume: 5 µL

Run time: NLT 1.2 times the retention time of gemifloxacin

3.3 System suitability

Sample: Standard solution

Suitability requirements

Resolution: NLT 5.0 between E-gemifloxacin and gemifloxacin

Tailing factor: NMT 1.5 for gemifloxacin

Relative standard deviation: NMT 1.0% for gemifloxacin

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of gemifloxacin mesylate (C₁₈H₂₀FN₅O₄·CH₄O₃S) in the portion of Gemifloxacin Mesylate taken:

Result = (r_U/r_S) x (C_S/C_U) x 100

r_U = peak response of gemifloxacin from the Sample solution

r_S = peak response of gemifloxacin from the Standard solution

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

C_U = concentration of Gemifloxacin Mesylate in the Sample solution (mg/mL)

Acceptance criteria: 98.0%-102.0% on the anhydrous and solvent-free basis

4 IMPURITIES

4.1 RESIDUE ON IGNITION (281)

NMT 0.1%

4.2 ORGANIC IMPURITIES

Store the solutions in amber vials and protect from light.

Solution A: Acetonitrile, water, and trifluoroacetic acid (20:80:0.1)

Solution B: Acetonitrile, water, and trifluoroacetic acid (80:20:0.1)

Mobile phase: See Table 1.

Table 1

Diluent: Acetonitrile and water (20:80)

Peak identification solution: 0.5 mg/mL of USP Gemifloxacin Mesylate RS, and 0.001 mg/mL each of USP Gemifloxacin Related Compound B RS and USP Gemifloxacin Related Compound C RS in Diluent. [NOTE-It is recommended to use freshly prepared USP Gemifloxacin Related Compound C RS.]

System suitability solution: 0.5 mg/mL of USP Gemifloxacin Mesylate RS in Diluent

Sensitivity solution: 0.25 µg/mL of USP Gemifloxacin Mesylate RS in Diluent

Standard solution: 0.0005 mg/mL of USP Gemifloxacin Mesylate RS in Diluent from the System suitability solution

Sample solution: 0.5 mg/mL of Gemifloxacin Mesylate in Diluent

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detectors

UV 207 nm: 0-5 min

UV 272 nm: 5.1-37 min

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

Column temperature: 40°

Flow rate: 1.0 mL/min

Injection volume: 5 µL

System suitability

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

Suitability requirements

Resolution: NLT 5.0 between E-gemifloxacin and gemifloxacin, System suitability solution

Relative standard deviation: NMT 10% for gemifloxacin, Standard solution

Signal-to-noise ratio: NLT 10, Sensitivity solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of each individual impurity in the portion of Gemifloxacin Mesylate taken:

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

r_U = peak response of each individual impurity from the Sample solution

r_S = peak response of gemifloxacin from the Standard solution

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

C_U = concentration of Gemifloxacin Mesylate in the Sample solution (mg/mL)

F = relative response factor (see Table 2)

Acceptance criteria: See Table 2. The reporting threshold is 0.05%.

Table 2

^a (Z)-4-(Aminomethyl)pyrrolidin-3-one O-methyl oxime dimethanesulfonate.

^b This impurity should be included, if present, in the synthetic route used by the manufacturer.

^c (E)-7-[3-(Aminomethyl)-4-(methoxyimino)pyrrolidin-1-yl]-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid monomethanesulfonate.

^d 7-Chloro-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid.

^e (Z)-7-({[1-(6-Carboxy-8-cyclopropyl-3-fluoro-5-oxo-5,8-dihydro-1,8-naphthyridin-2-yl)-4-(methoxyimino)pyrrolidin-3-yl]methyl}amino)-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid.

5 SPECIFIC TESTS

WATER DETERMINATION (921), Method I

Sample: 0.1 g

Acceptance criteria: 4.0%-7.0%

6 ADDITIONAL REQUIREMENTS

6.1 PACKAGING AND STORAGE

Store in tightly closed containers, protected from light. Store at room temperature.

6.2 USP REFERENCE STANDARDS (11)

USP Gemifloxacin Mesylate RS

USP Gemifloxacin Related Compound B RS

7-[3-(Aminomethyl)-4-hydroxypyrrolidin-1-yl]-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid monomethanesulfonate.

C₁₇H₁₉FN₄O₄·CH₄O₃S 458.46

USP Gemifloxacin Related Compound C RS

7-[3-(Aminomethyl)-4-oxopyrrolidin-1-yl]-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid monomethanesulfonate.

C₁₇H₁₇FN₄O₄·CH₄O₃S 456.45(USP 1-May-2021)