4834Levofloxacin / Official Monographs
USP 40
Acceptance criteria
ASSAY
Individual impurities: See Impurity Table 1.
•P ROCEDURE
Diluent: Acetonitrile and water (20:80)
Mobile pha: Transfer 874mg of cupric sulfate,
Impurity Table 1918mg of L -isoleucine, and 5.94g of ammonium ace-Relative Relative Acceptance tate to a suitable container. Add 700mL of water, and Retention Respon Criteria,mix until dissolved. Add 300mL of methanol.
Name
Time
Factor
NMT (%)
Standard stock solution: 2mg/mL of USP Levofloxacin 9-Desfluoro RS in Diluent
—*levofloxacin a 0.64 1.0Standard solution: 0.2mg/mL of USP Levofloxacin RS in Mobile pha from the Standard stock solution
Diamine —*
Sample stock solution: Nominally 5mg/mL of levoflox-derivative b 0.75
1.0
acin prepared as follows. Transfer intact Tablets (NLT 5)Levofloxacin to a volumetric flask, add 75% of the final volume of related
Diluent , and allow to stand for 15 min. Shake for 30compound A c 0.910.810.5min, and dilute with D
iluent to volume. Pass a portion Levofloxacin 1.0——of the solution through a suitable filter of 0.45-µm pore Levofloxacin size, discarding the first 1–2mL of the filtrate.
N -oxide d
1.550.930.5Sample solution: Nominally 0.2mg/mL of levofloxacin Any other individual in Mobile pha from the Sample stock solution —impurity
1.00.2Chromatographic system
Total impurities
—
—
1.0
(See Chromatography 〈621〉, System Suitability .)Mode: LC
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.
Detector: UV 360 nm
b (S )-9-Fluoro-2,3-dihydro-3-methyl-10-[2-(methylamino)ethylamino]-7-Column: 4.6-mm × 25-cm; 5-µm packing L1oxo-7H -pyrido[1,2,3-de ][1,4]benzoxazine-6-carboxyli
c acid.
Column temperature: 45°c (S )-9-Fluoro-2,3-dihydro-3-methyl-10-(piperazin-1-yl)-7-oxo-7H -pyrido[1,Flow rate: 0.8mL/min 2,3-de ][1,4]benzoxazine-6-carbocylic acid.
Injection volume: 25µL
反腐败
d (S )-4-(6-Carboxy-9-fluoro-2,3-dihydro-3-methyl-7-oxo-7H -pyrido-[1,2,3-Run time: 2 times th
e retention time o
f levofloxacin de ][1,4]benzoxazine-10-yl)-1-methylpiperazine 1-oxide.
System suitability
*Disregard this peak becau this is a process impurity controlled for the Sample: Standard solution drug substance.
Suitability requirements SPECIFIC TESTS
我喜欢的食物作文Tailing factor: NMT 1.8
•M ICROBIAL E NUMERATION T ESTS 〈61〉 and T ESTS F OR S PECI-Relative standard deviation: NMT 2.0%FIED M ICROORGANISMS 〈62〉: The total aerobic microbial Analysis
count does not exceed 102 cfu/mL, and the total com-Samples: Standard solution and Sample solution bined molds and yeast count does not exceed 101 cfu/Calculate the percentage of the labeled amount of mL. It also meets the requirement for abnce of Escher-levofloxacin (C 18H 20FN 3O 4) in the portion of Tablets ichia coli .
taken:
遗忘之前•D ELIVERABLE V OLUME 〈698〉: Meets the requirements •P H 〈791〉: 5.0–6.0
Result = (r U /r S ) × (C S /C U ) × 100
ADDITIONAL REQUIREMENTS
r U
= peak respon of levofloxacin from the Sample
•P ACKAGING AND S TORAGE : Store at controlled room tem-solution
perature, and protect from light.r S = peak respon of levofloxacin from the
•USP R EFERENCE S TANDARDS 〈11〉Standard solution
USP Levofloxacin RS
C S = concentration of USP Levofloxacin RS in the
7H -Pyrido[1,2,3-de ]-1,4-benzoxazine-6-carboxylic acid,Standard solution (mg/mL)
9-fluoro-2,3-dihydro-3-methyl-10-(4-methyl-1-piper-C U = nominal concentration of levofloxacin in the
azinyl)-7-oxo-hydrate (2:1), (S )-;
Sample solution (mg/mL)
(−)-(S )-9-Fluoro-2,3-dihydro-3-methyl-10-(4-methyl-Acceptance criteria: 90.0%–110.0%
1-piperazinyl)-7-oxo-7H -pyrido[1,2,3-de ]-1,4-benzox-azine-6-carboxylic acid, hemihydrate.PERFORMANCE TESTS Anhydrous.
•D ISSOLUTION 〈711〉C 18H 20FN 3O 4·1/2H 2O 370.38
Test 1
USP Levofloxacin Related Compound A RS
Medium: 0.1 N hydrochloric acid; 900mL (S )-9-Fluoro-2,3-dihydro-3-methyl-10-(piperazin-1-yl)-Apparatus 2: 75 rpm 7-oxo-7H -pyrido[1,2,3-de ][1,4]benzoxazine-6-carbo-Time: 30 min
cylic acid.Standard solution: 0.56mg/mL of USP Levofloxacin C 17H 18FN 3O 4347.34
RS in Medium
角开头的四字成语
Sample solution: Pass a portion of the solution under test through a suitable filter of 0.45-µm pore size.Instrumental conditions
(See Ultraviolet-Visible Spectroscopy 〈857〉.)Mode: UV
Levofloxacin Tablets
Analytical wavelength: 294 nm Cell length: 0.1mm DEFINITION
Blank: Medium Levofloxacin Tablets contain NLT 90.0% and NMT 110.0%Analysis
of the labeled amount of levofloxacin (C 18H 20FN 3O 4).Samples: Standard solution and Sample solution
IDENTIFICATION
Calculate the percentage (Q ) of the labeled amount of •A . The retention time of the major peak of the Sample levofloxacin (C 18H 20FN 3O 4) dissolved:
solution corresponds to that of the Standard solution , as Result = (A U /A S ) × C S × V × D × (1/L ) × 100
obtained in the Assay .
USP 40
Official Monographs / Levofloxacin 4835
A U = absorbance of the Sample solution Blank: Medium A S = absorbance of the Standard solution Analysis
C S
= concentration of the Standard solution
Samples: Standard solution and Sample solution
(mg/mL)
Calculate the percentage (Q ) of the labeled amount of V = volume of Medium , 900mL levofloxacin (C 18H 20FN 3O 4) dissolved:
D = dilution factor of the Sample solution Result = (A U /A S ) × C S × V × D × (1/L ) × 100
L = label claim (mg/Tablet)
Tolerances: NLT 80% (Q ) of the labeled amount of A U = absorbance of the Sample solution levofloxacin (C 18H 20FN 3O 4) is dissolved.A S = absorbance of the Standard solution Test 2
C S
= concentration of the Standard solution
Medium: 0.1 N hydrochloric acid; 900mL (mg/mL)
Apparatus 1: 100 rpm V = volume of Medium , 900mL Time: 30 min
D = dilution factor of the Sample solution Standard solution: L /900mg/mL of USP Levofloxacin L = label claim (mg/Tablet)
RS in Medium , and mix to obtain solutions with known Tolerances: NLT 80% (Q ) of the labeled amount of concentrations as indicated in Table 1, where L is the levofloxacin (C 18H 20FN 3O 4) is dissolved.label claim in mg/Tablet.
Test 4
Sample solution: Pass a portion of the solution under Medium: 0.1 N hydrochloric acid; 900mL test having a concentration similar to that of the Stan-Apparatus 1: 100 rpm dard solution through a suitable filter of 0.45-µm pore Time: 30 min
size.
Standard solution: 16µg/mL of USP Levofloxacin RS in Medium
Table 1
Sample solution: Pass a portion of the solution under test having the same concentration as that of the Stan-Tablet Label Claim
Final Concentration
dard soluiton through a suitable filter of 0.45-µm pore (mg)(mg/mL)size.
2500.27Instrumental conditions
5000.55(See Ultraviolet-Visible Spectroscopy 〈857〉.)750
0.83
Mode: UV
Analytical wavelength: 332 nm Instrumental conditions
Cell length: 1cm (See Ultraviolet-Visible Spectroscopy 〈857〉.)Blank: Medium Mode: UV
Analysis
Analytical wavelength: 293 nm Samples: Standard solution and Sample solution
Cell length: 0.1mm Calculate the percentage (Q ) of the labeled amount of Blank: Medium levofloxacin (C 18H 20FN 3O 4) dissolved:
Analysis
Samples: Standard solution and Sample solution
Result = (A U /A S ) × C S × V × D × (1/L ) × 100
Calculate the percentage (Q ) of the labeled amount of levofloxacin (C 18H 20FN 3O 4) dissolved:
怎么止鼻血A U = absorbance of the Sample solution A S = absorbance of the Standard solution Result = (A U /A S ) × C S × V × D × (1/L ) × 100
C S
= concentration of the Standard solution
(mg/mL)
A U = absorbance of the Sample solution V = volume of Medium , 900mL A S = absorbance of the Standard solution D = dilution factor of the Sample solution C S
= concentration of the Standard solution
L = label claim (mg/Tablet)
(mg/mL)
Tolerances: NLT 80% (Q ) of the labeled amount of V = volume of Medium , 900mL levofloxacin (C 18H 20FN 3O 4) is dissolved.D = dilution factor of the Sample solution •U NIFORMITY OF D OSAGE U NITS 〈905〉: Meet the L = label claim (mg/Tablet)
requirements Tolerances: NLT 80% (Q ) of the labeled amount of levofloxacin (C 18H 20FN 3O 4) is dissolved.IMPURITIES
Test 3
•O RGANIC I MPURITIES
Medium: 0.1 N hydrochloric acid; 900mL Diluent, Mobile pha, Standard stock solution, Sam-Apparatus 1: 100 rpm ple solution, and Chromatographic system: Proceed Time: 30 min
as directed in the Assay .
Standard solution: L /900mg/mL of USP Levofloxacin Standard solution: 0.2mg/mL of USP Levofloxacin RS RS in Medium , and mix to obtain solutions with known from the Standard stock solution and 1µg/mL of USP concentrations as indicated in Table 1, where L is the Levofloxacin Related Compound A RS in Mobile pha label claim in mg/Tablet.
System suitability
Sample solution: Pass a portion of the solution under Sample: Standard solution test having the same concentration as that of the Stan-Suitability requirements
dard solution through a suitable filter of 0.45-µm pore Tailing factor: NMT 1.8 for the levofloxacin peak size.
Relative standard deviation: NMT 2.0% for the Instrumental conditions
levofloxacin peak (See Ultraviolet-Visible Spectroscopy 〈857〉.)Analysis
Mode: UV
Samples: Standard solution and Sample solution
Analytical wavelength: 326 nm
Calculate the percentage of levofloxacin related com-Cell length: 1mm for a 250-mg Tablet, 0.5mm for a pound A in the portion of Tablets taken:
500-mg Tablet, and 0.2mm for a 750-mg Tablet
Result = (r U /r S ) × (C S /C U ) × 100
r U
= peak respon of levofloxacin related
compound A from the Sample solution
4836Levofloxacin / Official Monographs
USP 40
r S
= peak respon of levofloxacin related
•USP R EFERENCE S TANDARDS 〈11〉compound A from the Standard solution
USP Levofloxacin RS
C S = concentration of USP Levofloxacin Related
USP Levofloxacin Related Compound A RS
Compound A RS in the Standard solution (S )-9-Fluoro-3-methyl-10-(piperazin-1-yl)-7-oxo-2,3-(mg/mL)
dihydro-7H -pyrido[1,2,3-de ][1,4]benzoxazine-6-carbox-C U = nominal concentration of levofloxacin in the
ylic acid.Sample solution (mg/mL)
C 17H 18FN 3O 4347.34
Calculate the percentage of any other impurities in the portion of Tablets taken:
Result = (r U /r S ) × (C S /C U ) × (1/F ) × 100
Levonordefrin
r U
= peak respon of any impurity from the
Sample solution
r S = peak respon of levofloxacin from the
Standard solution
C S
= concentration of USP Levofloxacin RS in the
Standard solution (mg/mL)
C U = nominal concentration of levofloxacin in the
C 9H 13NO 3183.20
Sample solution (mg/mL)
1,2-Benzenediol, 4-(2-amino-1-hydroxypropyl)-, [R -(R *,S *)]-.F = relative respon factor (e Table 2)(-)-α-(1-Aminoethyl)-3,4-dihydroxybenzyl alcohol Acceptance criteria: See Table 2.
古诗宿建德江[18829-78-2; 829-74-3].
Table 2
» Levonordefrin, dried in vacuum at 60° for
15hours, contains not less than 98.0percent and Relative Relative Acceptance Retention Respon Criteria,not more than 102.0percent of C 9H 13NO 3.
Name
Time
Factor NMT (%)
Packaging and storage—Prerve in well-clod contain-Decarboxy ers.
levofloxacin a
0.380.600.3USP Reference standards 〈11〉—Levofloxacin related —USP Levonordefrin RS compound A b
0.470.7Identification—
Diamine derivative c 0.520.830.3A: Infrared Absorption 〈197K 〉.Levofloxacin N -oxide d 0.630.680.7B: Ultraviolet Absorption 〈197U 〉—9-Desfluoro Solution: 25µg per mL.
——f levofloxacin e 0.73Medium: 0.1 N hydrochloric acid.
Levofloxacin 1.00——Specific rotation 〈781S 〉: between −28° and −31°.
Dextrofloxacin g 1.23
——f Test solution: 50mg, previously dried, per mL, in 0.3 N Levofloxacin hydrochloric acid.
9-piperazino —
—f
Loss on drying 〈731〉—Dry it in vacuum at 60° for isomer h
1.6915hours: it los not more than 1.0% of its weight.Any unspecified —Residue on ignition 〈281〉: not more than 0.2%.impurity
1.00.2Chromatographic purity—
Total impurities
—
—
1Standard solutions—Dissolve an accurately weighed quan-a (S )-9-Fluoro-2,3-dihydro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-7H -
pyrido[1,2,3-de ][1,4]benzoxazine.
tity of USP Levonordefrin RS in a mixture of methanol and b (S )-9-Fluoro-3-methyl-10-(piperazin-1-yl)-7-oxo-2,3-dihydro-7H -pyrido[1,glacial acetic acid (96:4) to obtain a Standard stock solution 2,3-de ][1,4]benzoxazine-6-carboxylic acid.
having a known concentration of 5mg per mL. Dilute this c (S )-9-Fluoro-2,3-dihydro-3-methyl-10-[2-(methylamino)ethylamino]-7-solution quantitatively with a mixture of methanol and gla-oxo-7H -pyrido[1,2,3-de ][1,4]benzoxazine-6-carboxylic acid.
cial acetic acid (96:4) to obtain Standard solutions , desig-d (S )-4-(6-Carboxy-9-fluoro-2,3-dihydro-3-methyl-7-oxo-7H -pyrido-[1,2,3-nated below by letter, having the following compositions:
de ][1,4]benzoxazine-10-yl)-1-methylpiperazine 1-oxide.
e (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.Concentra-Percentage (%,
橄榄油的正确食用方法f Process impurity, for information only.
tion for comparison g (R )-9-Fluoro-2,3-dihydro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-7H -Standard (µg RS per
with test speci-pyrido[1,2,3-de ][1,4]benzoxazine-6-carboxylic acid.
做梦发大水solution
Dilution mL)men)h (S )-10-fluoro-3-methyl-9-(4-methylpiperazin-1-yl)-7-oxo-3,7-dihydro-7H -A (1 in 10)500 1.0pyrido[1,2,3-de ][1,4]benzoxazine-6-carboxylic acid.
B (1 in 20)2500.5ADDITIONAL REQUIREMENTS
C (1 in 50)1000.2•P ACKAGING AN
D S TORAG
E : Prerve in tight containers.D
(1 in 100)
50
0.1
Store at controlled room temperature.
•L ABELING : When more than one Dissolution test is given,the labeling states the Dissolution test ud only if Test 1Test solution—Dissolve an accurately weighed quantity of is not ud.
Levonordefrin in a mixture of methanol and glacial acetic acid (96:4) to obtain a solution containing 50mg per mL.Procedure— Apply parately 5µL of the Test solution and 5µL of each Standard solution to a suitable thin-layer chro-matographic plate (e Chromatography 〈621〉) coated with 0.25-mm layer of chromatographic silica gel mixture. Posi-tion the plate in a chromatographic chamber, and develop the chromatograms in a solvent system consisting of a mix-ture of n -butyl alcohol, water, and glacial acetic acid
