Add the following:
Levofloxacin Oral Solution
DEFINITION
Levofloxacin Oral Solution contains NLT 90.0% and NMT 110.0% of the labeled amount of levofloxacin (C18H20FN3O4).
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.
ASSAY
• Procedure
[Note—Protect the solutions of levofloxacin from light. ]
Diluent:
Acetonitrile and water (18:82)
Mobile phase:
Diluent that contains 1 mL of trifluoroacetic acid in each 1000 mL of solution
Standard solution:
102.5 µg/mL of USP Levofloxacin RS in Diluent
System suitability solution:
102.5 µg/mL each of USP Levofloxacin RS and USP Levofloxacin Related Compound A RS in Diluent
Sample solution:
102.5 µg/mL of levofloxacin 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
Mode:
LC
Detector:
UV 294 nm
Column:
4.6-mm × 15-cm; 3.5-µm packing L11
Column temperature:
30
Flow rate:
0.7 mL/min
Run time:
2.5 times the retention time of the levofloxacin peak
Injection size:
20 µL
System suitability
Samples:
Standard solution and System suitability solution
Suitability requirements
Resolution:
NLT 1.9 between levofloxacin related compound A and levofloxacin, System suitability solution
Relative standard deviation:
NMT 2.0%, Standard solution
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of the labeled amount of levofloxacin (C18H20FN3O4) in the portion of Oral Solution taken:
Result = (rU/rS) × (CS/CU) × 100
| rU | = | = peak response from the Sample solution |
| rS | = | = peak response from the Standard solution |
| CS | = | = concentration of USP Levofloxacin RS in the Standard solution (mg/mL) |
| CU | = | = nominal concentration of levofloxacin in the Sample solution (mg/mL) |
Acceptance criteria:
90.0%–110.0%
IMPURITIES
Organic Impurities
• Procedure
[Note—Protect the solutions of levofloxacin from light. ]
Diluent, Mobile phase, Standard solution, System suitability solution, Sample solution, Chromatographic system, and System suitability:
Proceed as directed in the Assay.
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of each individual impurity in the portion of Oral Solution taken:
Result = (rU/rS) × (CS/CU) × (1/F) × 100
| rU | = | = peak response of each individual impurity from the Sample solution |
| rS | = | = peak response of levofloxacin from the Standard solution |
| CS | = | = concentration of USP Levofloxacin RS in the Standard solution (mg/mL) |
| CU | = | = nominal concentration of levofloxacin in the Sample solution (mg/mL) |
| F | = | = relative response factor for each impurity (See Impurity Table 1) |
Acceptance criteria
Individual impurities:
See Impurity Table 1.
Impurity Table 1
| Name | Relative Retention Time |
Relative Response Factor |
Acceptance Criteria, NMT (%) |
|---|---|---|---|
| 9-Desfluoro levofloxacina |
0.64 | 1.0 | —* |
| Diamine derivativeb |
0.75 | 1.0 | —* |
| Levofloxacin related compound Ac |
0.91 | 0.81 | 0.5 |
| Levofloxacin | 1.0 | — | — |
| Levofloxacin N-oxided |
1.55 | 0.93 | 0.5 |
| Any other individual impurity | — | 1.0 | 0.2 |
| Total impurities | — | — | 1.0 |
|
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)-9-Fluoro-2,3-dihydro-3-methyl-10-(piperazin-1-yl)-7-oxo-7H-pyrido[1,2,3-de][1,4]benzoxazine-6-carbocylic 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.
*
Disregard this peak because this is a process impurity controlled for the drug substance.
|
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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.
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
698:
Meets the requirements
• pH 791:
5.0–6.0
791:
5.0–6.0
ADDITIONAL REQUIREMENTS
• Packaging and Storage:
Store at controlled room temperature, and protect from light.
• USP Reference Standards 11
11
USP Levofloxacin RS 
7H-Pyrido[1,2,3-de]-1,4-benzoxazine-6-carboxylic acid, 9-fluoro-2,3-dihydro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-hydrate (2:1), (S)-;
(
)-(S)-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, hemihydrate.
Anhydrous.
C18H20FN3O4·½H2O 370.38
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7H-Pyrido[1,2,3-de]-1,4-benzoxazine-6-carboxylic acid, 9-fluoro-2,3-dihydro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-hydrate (2:1), (S)-;
(
)-(S)-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, hemihydrate.
Anhydrous.
C18H20FN3O4·½H2O 370.38
USP Levofloxacin Related Compound A RS
(S)-9-Fluoro-2,3-dihydro-3-methyl-10-(piperazin-1-yl)-7-oxo-7H-pyrido[1,2,3-de][1,4]benzoxazine-6-carbocylic acid.
C17H18FN3O4 347.34
(S)-9-Fluoro-2,3-dihydro-3-methyl-10-(piperazin-1-yl)-7-oxo-7H-pyrido[1,2,3-de][1,4]benzoxazine-6-carbocylic acid.
C17H18FN3O4 347.34
USP35
Auxiliary Information—
Please check for your question in the FAQs before contacting USP.
| Topic/Question | Contact | Expert Committee |
|---|---|---|
| Monograph | Behnam Davani, Ph.D., M.B.A.
Senior Scientific Liaison 1-301-816-8394 |
(SM12010) Monographs - Small Molecules 1 |
| 61 |
Radhakrishna S Tirumalai, Ph.D.
Principal Scientific Liaison 1-301-816-8339 |
(GCM2010) General Chapters - Microbiology |
| 62 |
Radhakrishna S Tirumalai, Ph.D.
Principal Scientific Liaison 1-301-816-8339 |
(GCM2010) General Chapters - Microbiology |
| Reference Standards | RS Technical Services 1-301-816-8129 rstech@usp.org |
USP35–NF30 Page 3672
Pharmacopeial Forum: Volume No. 36(6) Page 1548