Moxifloxacin Hydrochloride

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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C₂₁H₂₄FN₃O₄ · HCl      437.89

(4aS-cis)-1-Cyclopropyl-6-fluoro-1,4-dihydro-8-methoxy-7-(octahydro-6H-pyrrolo[3,4-b]pyridin-6-yl)-4-oxo-3-quinolinecarboxylic acid, monohydrochloride;

1-Cyclopropyl-6-fluoro-1,4-dihydro-8-methoxy-7-[(4aS,7aS)-octahydro-6H-pyrrolo[3,4-b]pyridin-6-yl]-4-oxo-3-quinolinecarboxylic acid, monohydrochloride   CAS RN^®: 186826-86-8; UNII: C53598599T.

1 DEFINITION

Moxifloxacin Hydrochloride contains NLT 98.0% and NMT 102.0% of moxifloxacin hydrochloride (C₂₁H₂₄FN₃O₄ · HCl), calculated on the anhydrous basis.

2 IDENTIFICATION

Change to read:

A. ^▲SPECTROSCOPIC IDENTIFICATION TESTS (197), Infrared Spectroscopy: 197K _{▲(CN 1-MAY-2020)}

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

C. IDENTIFICATION TESTS-GENERAL (191), Chloride

Sample solution: To a solution (1 in 160) add diluted nitric acid, and filter.

Acceptance criteria: Meets the requirements

3 ASSAY

PROCEDURE

Buffer: Dissolve 0.5 g of tetrabutylammonium hydrogen sulfate and 1.0 g of monobasic potassium phosphate in water, add 2 mL of phosphoric acid, dilute with water to 1000 ml, mix, and pass through a filter of 0.45-µm pore size.

Mobile phase: Methanol and Buffer (28:72)

Diluent: Add 20 mg of anhydrous sodium sulfite to 1000 mL of Buffer, mix gently, and pass through a filter of 0.45-µm pore size.

System suitability solution: 0.1 mg/mL of USP Moxifloxacin Hydrochloride RS and 1 µg/mL of USP Moxifloxacin Related Compound A RS, in Diluent

Standard solution: 0.1 mg/mL of USP Moxifloxacin Hydrochloride RS in Diluent

Sample solution: 0.1 mg/mL of Moxifloxacin Hydrochloride in Diluent

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 293 nm

Column: 4.0-mm x 25-cm; 5-µm packing L11

Column temperature: 45°

Flow rate: 0.9 mL/min

Injection volume: 25 µL

System suitability

Samples: System suitability solution and Standard solution

[NOTE-The relative retention times for moxifloxacin and moxifloxacin related compound A are about 1.0 and 1.2, respectively.]

Suitability requirements

Resolution: NLT 1.5 between moxifloxacin and moxifloxacin related compound A, System suitability solution

Tailing factor: NMT 2.0, Standard solution

Relative standard deviation: NMT 0.73%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of moxifloxacin hydrochloride (C₂₁H₂₄FN₃O₄ · HCl) in the portion of Moxifloxacin Hydrochloride taken:

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

r_U = peak response from the Sample solution

r_S = peak response from the Standard solution

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

C_U = concentration of Moxifloxacin Hydrochloride in the Sample solution (mg/mL)

Acceptance criteria: 98.0%~102.0% on the anhydrous basis

4 IMPURITIES

4.1 RESIDUE ON IGNITION (281)

NMT 0.1%

4.2 CHLORIDE AND SULFATE (221), Sulfate

Sample: 0.6 g

Acceptance criteria: 0.04%; the Sample shows no more sulfate than corresponds to 0.25 mL of 0.020 N sulfuric acid.

4.3 ORGANIC IMPURITIES

Protect all solutions containing moxifloxacin from light.

Mobile phase, Diluent, System suitability solution, and Sample solution: Prepare as directed in the Assay.

Standard solution: 2 µg/mL of USP Moxifloxacin Hydrochloride RS in Diluent

Sensitivity solution: 0.05 µg/mL of USP Moxifloxacin Hydrochloride RS from the Standard solution in Diluent. Store the Sensitivity solution under refrigeration and protected from light.

Chromatographic system: Proceed as directed in the Assay with a run time of two times the retention time of moxifloxacin.

System suitability

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

Suitability requirements

Resolution: NLT 1.5 between moxifloxacin and moxifloxacin related compound A, System suitability solution

Tailing factor: NMT 2.0, Standard solution

Relative standard deviation: NMT 2.0%, Standard solution

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

Analysis

Samples: Sample solution and Standard solution

Calculate the percentage of each impurity in the portion of Moxifloxacin Hydrochloride taken:

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

r_U = peak response of each impurity from the Sample solution

r_S = peak response of moxifloxacin from the Standard solution s

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

C_U = concentration of Moxifloxacin Hydrochloride in the Sample solution (mg/mL)

F = relative response factor (see Table 1)

Acceptance criteria: See Table 1.

Table 1

^a 1-Cyclopropyl-6,8-difluoro-1,4-dihydro-7-[(4aS, 7aS)-octahydro-6H-pyrrolo[3,4-b]pyridin-6-yl]-4-oxo-3-quinolinecarboxylic acid.

^b 1-Cyclopropyl-6,8-dimethoxy-1,4-dihydro-7-[(4aS, 7aS)-octahydro-6H-pyrrolo[3,4-b]pyridin-6-yl]-4-oxo-3-quinolinecarboxylic acid.

^c 1-Cyclopropyl-8-ethoxy-6-fluoro-1,4-dihydro-7-[(4aS, 7aS)-octahydro-6H-pyrrolo[3,4-b]pyridin-6-yl]-4-oxo-3-quinolinecarboxylic acid.

^d 1-Cyclopropyl-8-fluoro-6-methoxy-1,4-dihydro-7-[(4aS,7aS)-octahydro-6H-pyrrolo[3,4-b]pyridin-6-yl]-4-oxo-3-quinolinecarboxylic acid.

^e1-Cyclopropyl-6-fluoro-8-hydroxy-1,4-dihydro-7-[(4aS,7aS)-octahydro-6H-pyrrolo[3,4-b]pyridin-6-yl]-4-oxo-3-quinolinecarboxylic acid.

4.4 ENANTIOMERIC PURITY

Protect all solutions containing moxifloxacin from light.

Buffer: 0.47 g/L of anhydrous cupric sulfate and 1.31 g/L of isoleucine in water. Adjust with 0.1 N sodium hydroxide to a pH of 4.50. AL

Solution A: Methanol and Buffer (500:1500)

Solution B: Methanol and Buffer (225:450)

Mobile phase: See Table 2.

Table 2

System suitability solution: 8 mg/mL of USP Moxifloxacin Hydrochloride RS and 8 µg/mL of USP Moxifloxacin Related Compound G RS in Solution A

Sensitivity solution: 0.8 µg/mL of USP Moxifloxacin Related Compound G RS in Solution A

Sample solution: 8 mg/mL of Moxifloxacin Hydrochloride in Solution A

Chromatographic system

(See Chromatography (621). System Suitability.)

Mode: LC

Detector: UV 295 nm

Column: 3.0-mm x 15-cm; 3-µm packing L1

Flow rate: 0.42 mL/min

Injection volume: 1.5 µL

System suitability

Samples: System suitability solution and Sensitivity solution

[NOTE-The relative retention times for moxifloxacin related compound G and moxifloxacin are 0.78 and 1.0, respectively.]

Suitability requirements

Resolution: NLT 2.0 between moxifloxacin related compound G and moxifloxacin, System suitability solution

Signal-to-noise ratio: NLT 5, Sensitivity solution

Analysis

Sample: Sample solution

Calculate the percentage of moxifloxacin related compound G in the portion of Moxifloxacin Hydrochloride taken:

                         Result = [r_U(r_U/r_S) ×] x 100

r_U = peak response of moxifloxacin related compound G from the Sample solution

r_S = peak response of moxifloxacin from the Sample solution

Acceptance criteria: NMT 0.15%

5 SPECIFIC TESTS

5.1 MICROBIAL ENUMERATION TESTS (61) and TESTS FOR SPECIFIED MICROORGANISMS (62)

Total aerobic microbial count: NMT 10³ cfu/g

Total combined molds and yeasts count: NMT 10² cfu/g

5.2 PH (791)

Sample solution: 2 mg/mL

Acceptance criteria: 3.9-4.6

5.3 WATER DETERMINATION (921), Method I. Method la

NMT 4.5%

6 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in tight, light-resistant containers. Store at room temperature.

USP REFERENCE STANDARDS (11)

USP Moxifloxacin Hydrochloride RS

USP Moxifloxacin Related Compound A RS

1-Cyclopropyl-6,8-difluoro-1,4-dihydro-7-[(4aS,7aS)-octahydro-6H-pyrrolo[3,4-b]pyridin-6-yl]-4-oxo-3-quinolinecarboxylic acid.

C₂₀H₂₁F₂N₃O₃          389.40

USP Moxifloxacin Related Compound G.RS

1-Cyclopropyl-6-fluoro-1,4-dihydro-8-methoxy-7-[(4aR,7aR)-octahydro-6H-pyrrolo[3,4-b]pyridin-6-yl]-4-oxo-3-quinolinecarboxylic acid, monohydrochloride.

C₂₁H₂₄FN₃O₄ · HCl    437.89