Moxifloxacin Ophthalmic 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

Moxifloxacin Ophthalmic Solution is a sterile, self-preserved aqueous solution of Moxifloxacin Hydrochloride. It contains NLT 90.0% and NMT 110.0% of the labeled amount of moxifloxacin (C₂₁H₂₄FN₃O₄).

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.

B. The UV absorption spectra of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

3 ASSAY

PROCEDURE

Solution A: Dissolve 0.5 g of tetrabutylammonium hydrogen sulfate and 1.0 g of monobasic potassium phosphate in 1000 mL of water. Add 2 mL of phosphoric acid, filter, and degas.

Solution B: Methanol

Mobile phase: See Table 1.

Table 1

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

Standard stock solution: 6 mg/mL of USP Moxifloxacin Hydrochloride RS in water

Standard solution: 0.1 mg/mL of USP Moxifloxacin Hydrochloride RS in Solution A from the Standard stock solution

Sample solution: Nominally 0.1 mg/mL of moxifloxacin from Ophthalmic Solution in Solution A

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 293 nm. For Identification B, use a diode array detector in the range of 200-400 nm.

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

Column temperature: 45°

Flow rate: See Table 1.

Injection volume: 25 µL

System suitability

Samples: System suitability solution and Standard solution

Suitability requirements

Resolution: NLT 2.0 between the moxifloxacin and moxifloxacin related compound A peaks, System suitability solution

Tailing factor: NMT 2.0, Standard solution

Relative standard deviation: NMT 2.0%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of moxifloxacin (C₂₁H₂₄FN₃O₄) in the portion of Ophthalmic Solution taken: 

                         Result = (r_U/r_S) × (C_S/C_U) × (M_r1/M_r2) ×100

r_U = peak response of moxifloxacin from the Sample solution

r_S = peak response of moxifloxacin from the Standard solution

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

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

M_r1 = molecular weight of moxifloxacin, 401.43

M_r2 = molecular weight of moxifloxacin hydrochloride, 437.89

Acceptance criteria: 90.0%-110.0%

4 IMPURITIES

4.1 ORGANIC IMPURITIES: EARLY-ELUTING RELATED COMPOUNDS (RELATIVE RETENTION LESS THAN 1.8)

Protect the System suitability solution, Sample solution, and Standard solution from light. Analyze the Sample solution immediately after preparation.

Solution A, Solution B, Mobile phase, System suitability solution, Standard stock solution, and Sample solution: Prepare as directed in the Assay.

Blank solution: Use Solution A.

Standard solution: 2 µg/mL of USP Moxifloxacin Hydrochloride RS in Solution A from the Standard stock solution

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

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: See Table 1.

Injection volume: 25 µL

System suitability

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

Suitability requirements

Resolution: NLT 2.0 between the moxifloxacin and moxifloxacin related compound A peaks, 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: Blank solution, Standard solution, and Sample solution

[NOTE-Determine the relative retention values (r) for components listed in Table 2, using the time measured at the first baseline deflection of the Standard solution chromatogram as the void volume (t))

Calculate the percentage of each impurity in the portion of Ophthalmic Solution taken:

                         Result = (r_U/r_S) × (C_S/C_U) × (M_r1/M_r2) × (1/F) × 100

r_U = peak response of each impurity from the Sample solution

r_S = peak response of moxifloxacin from the Standard solution 

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

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

M_r1 = molecular weight of moxifloxacin, 401.43

M_r2 = molecular weight of moxifloxacin hydrochloride, 437.89

F = relative response factor (see Table 2)

Acceptance criteria: See Table 2. 

^a 1-Cyclopropyl-6-fluoro-8-methoxy-7-[(4aS,7aS)-octahydro-pyrrolo[3,4-b]pyridin-6-yl)-1H-quinolin-4-one.

^b Disregard this peak because this is a process impurity controlled for the drug substance.

^c 1-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.

^d Disregard this peak because it is quantitated using Organic Impurities: Late-Eluting Related Compounds (Relative Retention Equal to More Than 1.8).

4.2 ORGANIC IMPURITIES: LATE-ELUTING RELATED COMPOUNDS (RELATIVE RETENTION EQUAL TO MORE THAN 1.8)

Protect the Standard solution and Sample solution from light. Analyze the Sample solution immediately after preparation.

Solution A, Solution B, and Standard stock solution: Prepare as directed in the Assay.

Mobile phase: Solution A and Solution B (60:40)

Blank solution: Use Solution A.

Standard solution: 2 µg/mL of USP Moxifloxacin Hydrochloride RS in Solution A from the Standard stock solution

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

Sample solution: Nominally 0.1 mg/mL of moxifloxacin from Ophthalmic Solution in Solution A. The 8-hydroxy compound is unstable in dilute aqueous solutions.

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

Run time: NLT 5 times the retention time of moxifloxacin peak

System suitability

Samples: Standard solution and Sensitivity solution

Suitability requirements

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: Blank solution, Standard solution, and Sample solution

[NOTE-Determine the relative retention values (r) for components listed in Table 3, using the time measured at the first baseline deflection of the Standard solution chromatogram as the void volume (t_M).]

Calculate the percentage of each impurity in the portion of Ophthalmic Solution taken:

                         Result = (r_U/r_S) × (C_S/C_U) × (M_r1/M_r2) × (1/F) x 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) ng/mL)

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

M_r1 = molecular weight of moxifloxacin, 401.43

M_r2 = molecular weight of moxifloxacin hydrochloride, 437.89

F = relative response factor (see Table 3)

Acceptance criteria: See Table 3.

Table 3

^a 7-Amino-1-cyclopropyl-6-fluoro-8-methoxy-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid.

Total impurities: NMT 1.5%, sum from both Organic Impurities tests

5 SPECIFIC TESTS

STERILITY TESTS (71), Test for Sterility of the Product to Be Examined, Membrane Filtration: Meets the requirements

PH (791): 6.3-7.9

OSMOLALITY AND OSMOLARITY (785): 260-370 mOsmol/kg

6 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in tight containers. Store between 2 and 25°.

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