Printed on: Sun Aug 07 2022, 10:45:12 PM(EST) Status: Currently Official on 08-Aug-2022 DocId: GUID-6BE4948A-0EC7-4D29-96E9-CAD18B45317A_4_en-US

Printed by: Mahakam Beta Farma Official Date: Official as of 01-May-2020 Document Type: USP @2022 USPC
DOI Ref: vi67k DOI: https://doi.org/10.31003/USPNF_M14149_04_01
1

Suitability requirements
Ceftriaxone for Injection Resolution: NLT 3.0 between the ceftriaxone and
DEFINITION ceftriaxone E-isomer peaks, System suitability solution
Ceftriaxone for Injection contains an amount of Ceftriaxone Tailing factor: NMT 2, Standard solution
Sodium equivalent to NLT 776 µg/mg of ceftriaxone Relative standard deviation: NMT 0.7%, Standard
(C18H18N8O7S3), calculated on the anhydrous basis, and the solution
Analysis
equivalent of NLT 90.0% and NMT 115.0% of the labeled
Samples: Standard solution, Sample solution 1, and Sample
amount of ceftriaxone (C18H18N8O7S3).
solution 2 or Sample solution 3
IDENTIFICATION Calculate the quantity, in µg/mg, of ceftriaxone
(C18H18N8O7S3) in the portion of Ceftriaxone for Injection
Change to read: taken:
• A. ▲SPECTROSCOPIC IDENTIFICATION TESTS á197ñ, Infrared Result = (r U/r S) × (C S/C U) × P
Spectroscopy: 197K▲ (CN 1-May-2020)
• B. The retention time of the major peak of the Sample rU = peak response of ceftriaxone from Sample
solution corresponds to that of the Standard solution, as solution 1
obtained in the Assay. rS = peak response of ceftriaxone from the Standard
ASSAY solution
• PROCEDURE CS = concentration of USP Ceftriaxone Sodium RS in
Protect solutions containing ceftriaxone sodium from light. the Standard solution (mg/mL)
Solution A: 9 g/L of monobasic potassium phosphate in CU = nominal concentration of ceftriaxone in Sample
solution 1 (mg/mL)

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water
Solution B: 24 g/L of dibasic sodium phosphate, P = potency of ceftriaxone in USP Ceftriaxone
dodecahydrate in water Sodium RS (µg/mg)
Solution C: 20 g/L of citric acid in water. Adjust with 10 N
sodium hydroxide TS to a pH of 5.0 prior to dilution. Acceptance criteria: NLT 776 µg/mg on the anhydrous
basis
Buffer: Combine 389 mL of Solution A and 611 mL of
Solution B. Adjust with 10 N sodium hydroxide TS or
phosphoric acid to a pH of 7.0.
Mobile phase: Dissolve 2.0 g each of tetradecylammonium
ci Calculate the percentage of the labeled amount of
ceftriaxone (C18H18N8O7S3) in the portion of Ceftriaxone
for Injection withdrawn from the container or in the
bromide and tetraheptylammonium bromide in a mixture portion of the constituted solution:
of 440 mL of water, 55 mL of Buffer, 5.0 mL of Solution C,
ffi
and 500 mL of acetonitrile. Result = (r U/r S) × (C S/C U) × P × F × 100
System suitability solution: 50 µg/mL each of USP
rU = peak response of ceftriaxone from Sample solution
Ceftriaxone Sodium RS and USP Ceftriaxone Sodium
2 or Sample solution 3
E-Isomer RS in Mobile phase
rS = peak response of ceftriaxone from the Standard
Standard solution: 0.3 mg/mL of USP Ceftriaxone
solution
Sodium RS in Mobile phase
O

CS = concentration of USP Ceftriaxone Sodium RS in

Sample solution 1: Nominally 0.3 mg/mL of ceftriaxone
the Standard solution (mg/mL)
from Ceftriaxone for Injection in Mobile phase
CU = nominal concentration of ceftriaxone in Sample
Sample solution 2 (where it is represented as being in a
solution 2 or Sample solution 3 (mg/mL)
single-dose container): Nominally 0.3 mg/mL of
P = potency of ceftriaxone in USP Ceftriaxone
ceftriaxone in Mobile phase prepared as follows. Constitute
Sodium RS (µg/mg)
Ceftriaxone for Injection in a volume of water
F = conversion factor, 0.001 mg/µg
corresponding to the volume of solvent specified in the
labeling. Withdraw all of the withdrawable contents using a Acceptance criteria: 90.0%–115.0% of the labeled amount
suitable hypodermic needle and syringe, and transfer to a of ceftriaxone
suitable volumetric flask. Dilute with Mobile phase to
volume. PERFORMANCE TESTS
Sample solution 3 (where the label states the quantity of • UNIFORMITY OF DOSAGE UNITS á905ñ: Meets the
ceftriaxone in a given volume of constituted solution): requirements
Nominally 0.3 mg/mL of ceftriaxone in Mobile phase
prepared as follows. Constitute Ceftriaxone for Injection IMPURITIES
in a volume of water corresponding to the volume of • ORGANIC IMPURITIES
solvent specified in the labeling, and dilute with Protect solutions containing ceftriaxone sodium from light.
Mobile phase to final volume. Solution A, Solution B, Solution C, Buffer, Mobile phase,
Chromatographic system System suitability solution, and Chromatographic
(See Chromatography á621ñ, System Suitability.) system: Proceed as directed in the Assay.
Mode: LC Standard solution: 3 µg/mL of USP Ceftriaxone Sodium RS
Detector: UV 254 nm in Mobile phase
Column: 4.6-mm × 25-cm; 5-µm packing L1 Sample solution: Nominally 0.3 mg/mL of ceftriaxone from
Flow rate: 1.5 mL/min Ceftriaxone for Injection in Mobile phase
Injection volume: 20 µL System suitability
System suitability Sample: System suitability solution
Samples: System suitability solution and Standard solution [NOTE—The relative retention times for ceftriaxone and
[NOTE—The relative retention times for ceftriaxone and ceftriaxone E-isomer are listed in Table 1.]
ceftriaxone E-isomer are 1.0 and 1.4, respectively.]

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Printed on: Sun Aug 07 2022, 10:45:12 PM(EST) Status: Currently Official on 08-Aug-2022 DocId: GUID-6BE4948A-0EC7-4D29-96E9-CAD18B45317A_4_en-US
Printed by: Mahakam Beta Farma Official Date: Official as of 01-May-2020 Document Type: USP @2022 USPC
DOI Ref: vi67k DOI: https://doi.org/10.31003/USPNF_M14149_04_01
2

Suitability requirements b Process impurities that are controlled in the drug substance are not to be
Resolution: NLT 3.0 between the ceftriaxone and reported, are not included in total impurities, and are listed here for
information only.
ceftriaxone E-isomer c 3-Mercapto-2-methyl-1,2-dihydro-1,2,4-triazine-5,6-dione.
Analysis d (Z)-S-Benzothiazol-2-yl 2-(2-aminothiazol-4-yl)-2-(methoxyimino)
Samples: Standard solution and Sample solution thioacetate.
Calculate the percentage of each individual impurity in the e (6R,7R)-7-Amino-3-{[(6-hydroxy-2-methyl-5-oxo-2,5-dihydro-1,2,4-triazin-3-
portion of Ceftriaxone for Injection taken: yl)thio]methyl}-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid.
f (6R,7R)-7-[(Z)-2-(2-Aminothiazol-4-yl)-2-(methoxyimino)acetamido]-3-{[(6-
Result = (r U/r S) × (C S/C U) × P × F × 100 hydroxy-2-methyl-5-oxo-2,5-dihydro-1,2,4-triazin-3-yl)thio]methyl}-8-oxo-5-
thia-1-azabicyclo[4.2.0]oct-3-ene-2-carboxylic acid.
g (6R,7R)-7-[(E)-2-(2-Aminothiazol-4-yl)-2-(methoxyimino)acetamido]-3-{[(6-
rU = peak response of each individual impurity from hydroxy-2-methyl-5-oxo-2,5-dihydro-1,2,4-triazin-3-yl)thio]methyl}-8-oxo-5-
the Sample solution thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid.
rS = peak response of ceftriaxone from the Standard
solution SPECIFIC TESTS
CS = concentration of USP Ceftriaxone Sodium RS in • CONSTITUTED SOLUTION: At the time of use, it meets the
the Standard solution (mg/mL) requirements for Injections and Implanted Drug Products á1ñ,
CU = nominal concentration of ceftriaxone in the Product Quality Tests Common to Parenteral Dosage Forms,
Sample solution (mg/mL) Specific Tests, Completeness and clarity of solutions.
P = potency of ceftriaxone in USP Ceftriaxone • BACTERIAL ENDOTOXINS TEST á85ñ: NMT 0.20 USP
Sodium RS (µg/mg) Endotoxin Units/mg of ceftriaxone
F = conversion factor, 0.001 mg/µg • STERILITY TESTS á71ñ, Test for Sterility of the Product to Be
Examined, Membrane Filtration: It meets the requirements.
Acceptance criteria: See Table 1. Disregard any peak below • PARTICULATE MATTER IN INJECTIONS á788ñ: Meets the

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0.1%. requirements for small-volume injections
• CRYSTALLINITY á695ñ: Meets the requirements
Table 1 • PH á791ñ
Relative Acceptance Sample solution: 100 mg/mL
Retention Criteria, Acceptance criteria: 6.0–8.0
Name

Deacetylcefotaxime lactonea

7-Aminocephalosporan-
Time

0.20
NMT (%)

0.5
ci • WATER DETERMINATION á921ñ, Method I: 8.0%–11.0%
• OTHER REQUIREMENTS: It meets the requirements for
Labeling á7ñ, Labels and Labeling for Injectable Products.
—
ic acidb 0.34 ADDITIONAL REQUIREMENTS
ffi
Ceftriaxone triazine • PACKAGING AND STORAGE: Preserve as described in
analogc 0.62 1.0 Packaging and Storage Requirements á659ñ, Injection
Packaging, Packaging for constitution, and protected from
Ceftriaxone benzothiazolyl
oximed 0.72 0.2 light.
• USP REFERENCE STANDARDS á11ñ
Deacyl ceftriaxonee 0.78 1.0 USP Ceftriaxone Sodium RS
O

Ceftriaxone 1.0 — USP Ceftriaxone Sodium E-Isomer RS

(6R,7R)-7-[(E)-2-(2-Aminothiazol-4-yl)-2-
Ceftriaxone-3-ene isomerf 1.3 0.3 (methoxyimino)acetamido]-3-{[(6-hydroxy-2-methyl-5-
Ceftriaxone E-isomerg 1.4 1.0 oxo-2,5-dihydro-1,2,4-triazin-3-yl)thio]methyl}-8-oxo-
5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid,
Any individual disodium salt.
—
unspecified impurity 0.2
C18H16N8Na2O7S3 598.53
Total impurities — 5.0

a (Z)-2-(2-Aminothiazol-4-yl)-N-{(5aR,6R)-1,7-dioxo-1,3,4,5a,6,7-
hexahydroazeto[2,1-b]furo[3,4-d][1,3]thiazin-6-yl}-2-(methoxyimino)
acetamide.

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