Printed on: Thu Jul 15 2021, 06:36:50 PM Official Status: Currently Official on 15-Jul-2021 DocId: 1_GUID-B5371962-45A0-47EF-AF94-893AE6491783_2_en-US

(EST)
Printed by: Nguyen Nhan Official Date: Official as of 01-May-2021 Document Type: USP @2021 USPC
1

Add the following: Result = (rU/rS) × (CS/CU) × 100

rU = peak response of gemifloxacin from the Sample

▲
Gemifloxacin Mesylate solution
rS = peak response of gemifloxacin from the Standard
solution
CS = concentration of USP Gemifloxacin Mesylate RS
in the Standard solution (mg/mL)
CU = concentration of Gemifloxacin Mesylate in the
Sample solution (mg/mL)

Acceptance criteria: 98.0%–102.0% on the anhydrous and

solvent-free basis
IMPURITIES
C18H20FN5O4 · CH4O3S 485.49 • RESIDUE ON IGNITION á281ñ: NMT 0.1%
(Z)-7-[3-(Aminomethyl)-4-(methoxyimino)-1-pyrrolidinyl]-1- • ORGANIC IMPURITIES
cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-1,8-naphthyridine- Store the solutions in amber vials and protect from light.
3-carboxylic acid monomethanesulfonate; Solution A: Acetonitrile, water, and trifluoroacetic acid (20:
(±)-7-[3-(Aminomethyl)-4-oxo-1-pyrrolidinyl]-1-cyclopropyl- 80: 0.1)
6-fluoro-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic Solution B: Acetonitrile, water, and trifluoroacetic acid (80:
acid, 74-(Z)-(O-methyloxime), monomethanesulfonate; 20: 0.1)
(Z)-7-[3-(Aminomethyl)-4-(methoxyimino)pyrrolidin-1-yl]-1- Mobile phase: See Table 1.

al
cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-1,8-naphthyridine-
3-carboxylic acid methanesulfonate [210353-53-0]. Table 1
DEFINITION Time Solution A Solution B
(min) (%) (%)
Gemifloxacin Mesylate contains NLT 98.0% and NMT 102.0%
of gemifloxacin mesylate (C18H20FN5O4 · CH4O3S), calculated 0 100 0
on the anhydrous and solvent-free basis.
IDENTIFICATION
• A. SPECTROSCOPIC IDENTIFICATION TESTS á197ñ, Infrared
ci 15

35
100

0
0

100

Spectroscopy: 197K or 197M 37 100 0

ffi
• B. The retention time of the major peak of the Sample
solution corresponds to that of the Standard solution, as Diluent: Acetonitrile and water (20:80)
obtained in the Assay. Peak identification solution: 0.5 mg/mL of USP
ASSAY Gemifloxacin Mesylate RS, and 0.001 mg/mL each of USP
• PROCEDURE Gemifloxacin Related Compound B RS and USP
Store the solutions in amber vials and protect from light. Gemifloxacin Related Compound C RS in Diluent. [NOTE—It
O

Mobile phase: Acetonitrile, water, and trifluoroacetic acid is recommended to use freshly prepared USP Gemifloxacin
(20: 80: 0.1) Related Compound C RS.]
Standard solution: 0.5 mg/mL of USP Gemifloxacin System suitability solution: 0.5 mg/mL of USP
Mesylate RS in water Gemifloxacin Mesylate RS in Diluent
Sample solution: 0.5 mg/mL of Gemifloxacin Mesylate in Sensitivity solution: 0.25 µg/mL of USP Gemifloxacin
water Mesylate RS in Diluent
Chromatographic system Standard solution: 0.0005 mg/mL of USP Gemifloxacin
(See Chromatography á621ñ, System Suitability.) Mesylate RS in Diluent from the System suitability solution
Mode: LC Sample solution: 0.5 mg/mL of Gemifloxacin Mesylate in
Detector: UV 272 nm Diluent
Chromatographic system
Column: 4.6-mm × 25-cm; 5-µm packing L1
(See Chromatography á621ñ, System Suitability.)
Column temperature: 40°
Mode: LC
Flow rate: 1 mL/min
Detectors
Injection volume: 5 µL
UV 207 nm: 0–5 min
Run time: NLT 1.2 times the retention time of
UV 272 nm: 5.1–37 min
gemifloxacin
Column: 4.6-mm × 25-cm; 5-µm packing L1
System suitability
Column temperature: 40°
Sample: Standard solution
Flow rate: 1.0 mL/min
Suitability requirements
Resolution: NLT 5.0 between E-gemifloxacin and Injection volume: 5 µL
gemifloxacin System suitability
Tailing factor: NMT 1.5 for gemifloxacin Samples: System suitability solution, Sensitivity solution, and
Standard solution
Relative standard deviation: NMT 1.0% for
Suitability requirements
gemifloxacin
Resolution: NLT 5.0 between E-gemifloxacin and
Analysis
gemifloxacin, System suitability solution
Samples: Standard solution and Sample solution
Calculate the percentage of gemifloxacin mesylate Relative standard deviation: NMT 10% for
(C18H20FN5O4 · CH4O3S) in the portion of Gemifloxacin gemifloxacin, Standard solution
Signal-to-noise ratio: NLT 10, Sensitivity solution
Mesylate taken:

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Printed on: Thu Jul 15 2021, 06:36:50 PM Official Status: Currently Official on 15-Jul-2021 DocId: 1_GUID-B5371962-45A0-47EF-AF94-893AE6491783_2_en-US
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Printed by: Nguyen Nhan Official Date: Official as of 01-May-2021 Document Type: USP @2021 USPC
2

Analysis Table 2 (continued)

Samples: Standard solution and Sample solution Detection
Calculate the percentage of each individual impurity in the Relative Wave- Relative Acceptance
portion of Gemifloxacin Mesylate taken: Retention length Response Criteria,
Name Time (nm) Factor NMT (%)
Result = (rU/rS) × (CS/CU) × (1/F) × 100 Any other individu-
—
al impurity 272 1.0 0.1
rU = peak response of each individual impurity from Total impurities — — — 1.5
the Sample solution
rS = peak response of gemifloxacin from the Standard a (Z)-4-(Aminomethyl)pyrrolidin-3-one O-methyl oxime dimethanesulfonate.
solution b This impurity should be included, if present, in the synthetic route used by the
CS = concentration of USP Gemifloxacin Mesylate RS manufacturer.
in the Standard solution (mg/mL) c (E)-7-[3-(Aminomethyl)-4-(methoxyimino)pyrrolidin-1-yl]-1-cyclopropyl-6-

CU = concentration of Gemifloxacin Mesylate in the fluoro-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid

monomethanesulfonate.
Sample solution (mg/mL) d 7-Chloro-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-1,8-naphthyridine-3-
F = relative response factor (see Table 2) carboxylic acid.
e (Z)-7-({[1-(6-Carboxy-8-cyclopropyl-3-fluoro-5-oxo-5,8-dihydro-1,8-
Acceptance criteria: See Table 2. The reporting threshold is naphthyridin-2-yl)-4-(methoxyimino)pyrrolidin-3-yl]methyl}amino)-1-
0.05%. cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid.

Table 2 SPECIFIC TESTS

Detection
• WATER DETERMINATION á921ñ, Method I
Sample: 0.1 g

al
Relative Wave- Relative Acceptance
Retention length Response Criteria, Acceptance criteria: 4.0%–7.0%
Name Time (nm) Factor NMT (%)
ADDITIONAL REQUIREMENTS
Gemifloxacin relat-
ed com-
• PACKAGING AND STORAGE: Store in tightly closed
pound Aa, b 0.16 207 0.43 0.15 containers, protected from light. Store at room
temperature.
Gemifloxacin relat-
ed compound B

Gemifloxacin relat-
0.33 272 1.0
ci0.2
• USP REFERENCE STANDARDS á11ñ
USP Gemifloxacin Mesylate RS
USP Gemifloxacin Related Compound B RS
ed compound C 0.37 272 1.0 0.1 7-[3-(Aminomethyl)-4-hydroxypyrrolidin-1-yl]-1-
cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-1,8-
ffi
Gemifloxacin E-iso-
merc 0.77 272 1.0 0.7 naphthyridine-3-carboxylic acid
monomethanesulfonate.
Gemifloxacin 1.0 272 — —
C17H19FN4O4 · CH4O3S 458.46
Naphthyridine car- USP Gemifloxacin Related Compound C RS
boxylic acid ana- 7-[3-(Aminomethyl)-4-oxopyrrolidin-1-yl]-1-cyclopropyl-
logb, d 1.79 272 0.45 0.15
6-fluoro-4-oxo-1,4-dihydro-1,8-naphthyridine-3-
O

Gemifloxacin dim- carboxylic acid monomethanesulfonate.

ere 1.97 272 0.90 0.15 C17H17FN4O4 · CH4O3S 456.45▲ (USP 1-May-2021)

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