© 2011 USPC Official 8/1/11 - 11/30/11 USP Monographs: Levofloxacin

http://www.uspnf.com/uspnf/pub/data/v34291/usp34nf29s1_m2861.xml

Add the following: Levofloxacin (lee'' voe flox' a sin).

C18H20FN3O 4·½H2O oxo-hydrate (2:1), (S)-;

370.38

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-

( )-(S)-9-Fluoro-2,3-dihydro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-7H-pyrido[1,2,3-de]-1,4-benzoxazine6-carboxylic acid, hemihydrate Anhydrous DEFINITION Levofloxacin contains NLT 98.5% and NMT 102.0% of C18H20FN3O 4, calculated on the anhydrous basis. IDENTIFICATION • A. INFRARED ABSORPTION obtained in the Assay. ASSAY • PROCEDURE Solution A: 8.5 g/L of ammonium acetate, 1.25 g/L of cupric sulfate, pentahydrate, and 1.3 g/L of L-isoleucine in water Mobile phase: Methanol and Solution A (3:7) Standard solution: 1 mg/mL of USP Levofloxacin RS in Mobile phase Sample solution: 1 mg/mL of Levofloxacin in Mobile phase Chromatographic system (See Chromatography Mode: LC Detector: UV 360 nm Column: 4.6-mm × 25-cm; 5-µm packing L1 Column temperature: 45 Flow rate: 0.8 mL/min Injection size: 25 µL 621 , System Suitability.) 197K [100986-85-41]. [138199-71-0].

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

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[NOTE— Do not include the D-isomer in the calculation for Total 2 of 4 10/18/2011 3:19 PM .3 µg/mL of USP Levofloxacin RS in Mobile phase System suitability Samples: System suitability solution and Sensitivity solution Suitability requirements Relative standard deviation: NMT 1. Total impurities: NMT 0.0% Analysis Samples: Standard solution and Sample solution Calculate the percentage of C18H20FN3O 4 in the portion of Levofloxacin taken: Result = (r U/rS) × (CS/CU) × 100 rU rS CS CU = = peak response of Levofloxacin from the Sample solution = = peak response of levofloxacin from the Standard solution = = concentration of USP Levofloxacin RS in the Standard solution (mg/mL) = = concentration of Levofloxacin in the Sample solution (mg/mL) Acceptance criteria: 98.5 Relative standard deviation: NMT 1. Sensitivity solution Analysis Sample: Sample solution Calculate the percentage of each individual impurity in the portion of Levofloxacin taken: Result = (r U/rS) × (1/F) × 100 rU rS F = = peak area response of each impurity = = peak area response of levofloxacin = = relative response factor (see Impurity Table 1) Acceptance criteria Individual impurities: See Impurity Table 1.5%–102. System suitability solution Signal-to-noise ratio: NLT 10.5%. Method II Organic Impurities • PROCEDURE Solution A.5–1. Use a platinum crucible.© 2011 USPC Official 8/1/11 . 231 : NMT 10 ppm • HEAVY M ETALS . Mobile phase.xml System suitability Sample: Standard solution Suitability requirements Tailing factor: 0.11/30/11 USP Monographs: Levofloxacin http://www.0%. System suitability solution: 1 mg/mL of USP Levofloxacin RS in Mobile phase Sensitivity solution: 0.com/uspnf/pub/data/v34291/usp34nf29s1_m2861. and Chromatographic system: Proceed as directed in the Assay. Sample solution.2%.0% on the anhydrous basis IMPURITIES Inorganic Impurities • RESIDUE ON IGNITION 281 : NMT 0.uspnf.

2. Ph.4]benzoxazine-6-carboxylic acid.0 Acceptance Criteria. NMT (%) 0.3-dihydro-3-methyl-10-(piperazin-1-yl)-7-oxo-7H-pyrido[1.47 0.3-dihydro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-7H-pyrido[1.3 — 0.8 0. b (S)-9-Fluoro-2. e (R)-9-Fluoro-2.3-dihydro-3-methyl-10-[2-(methylamino)ethylamino]-7-oxo-7Hpyrido[1. c (S)-4-(6-Carboxy-9-fluoro-2. Senior Scientific Liaison Expert Committee (SM12010) Monographs .3-de][1.uspnf.3de][1.4]benzoxazine-6-carboxylic acid.A.73 1.2.D.Small Molecules 1 3 of 4 10/18/2011 3:19 PM .9 1.3 0.3-Dihydro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-7H-pyrido[1. ] Impurity Table 1 Name N-Desmethyl levofloxacina Diamine derivativeb Levofloxacin N-oxidec 9-Desfluoro levofloxacind Levofloxacin D-Isomer e Relative Retention Time 0. Store at room temperature.7% 781S • W ATER DETERMINATION . • USP REFERENCE STANDARDS USP Levofloxacin RS USP34 11 Auxiliary Information— Please check for your question in the FAQs before contacting USP.52 0.4]benzoxazine-10-yl)-1-methyl-piperazine-1-oxide.1 1.3 0.0 — 1.3de][1. d (S)-2. Method Ia ADDITIONAL REQUIREMENTS • PACKAGING AND STORAGE : Preserve in tight and light-resistant containers.4]benzoxazine-6-carboxylic acid.4]benzoxazine-6-carboxylic acid.3de][1..B. Specific Rotation Solvent: Methanol Sample solution: 5 mg/mL in Solvent Acceptance criteria: 92 to 106 .0 1. at 20 921 : 2.com/uspnf/pub/data/v34291/usp34nf29s1_m2861.© 2011 USPC Official 8/1/11 .63 0.2. M.23 — Relative Response Factor 1.0 0.0 1. SPECIFIC TESTS • O PTICAL ROTATION .2.3de][1. Topic/Question Monograph Contact Behnam Davani.3-dihydro-3-methyl-7-oxo-7H-pyrido-[1.11/30/11 USP Monographs: Levofloxacin http://www.3 0.2.1 Any unknown impurity a (S)-9-Fluoro-2.xml impurities.1%–2.

35(6) Page 1459 Chromatographic Column— LEVOFLOXACIN Chromatographic columns text is not derived from. USP 34 or NF 29.uspnf.11/30/11 USP Monographs: Levofloxacin http://www. and not part of. 4 of 4 10/18/2011 3:19 PM .com/uspnf/pub/data/v34291/usp34nf29s1_m2861.xml Topic/Question Reference Standards USP34–NF29 Page 3296 Contact 1-301-816-8394 RS Technical Services 1-301-816-8129 rstech@usp.© 2011 USPC Official 8/1/11 .org Expert Committee Pharmacopeial Forum: Volume No.