Cefdinir
(sef' di nir).
Click to View Image

C14H13N5O5S2 395.41
5-Thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid, 7-[[(2-amino-4-thiazolyl)(hydroxyimino)acetyl]amino]-3-ethenyl-8-oxo-, [6R-[6,7(Z)]]-;    
()-(6R,7R)-7-[2-(2-Amino-4-thiazolyl)glyoxylamido]-8-oxo-3-vinyl-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid, 72-(Z)-oxime     [91832-40-5].
DEFINITION
Cefdinir contains NLT 940 µg/mg and NMT 1030 µg/mg of cefdinir (C14H13N5O5S2), calculated on the anhydrous basis.
IDENTIFICATION
•  B. 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
Solution A:  14.2 g/L of anhydrous dibasic sodium phosphate
Solution B:  13.6 g/L of monobasic potassium phosphate
Solution C:  Dilute tetramethylammonium hydroxide (10%) with water to obtain a 0.1% solution. Adjust with 10% phosphoric acid to a pH of 5.5.
Solution D:  37.2 mg/mL of edetate disodium
Buffer:  Combine appropriate amounts of Solution A and Solution B (about 2:1) to obtain a solution with a pH of 7.0.
Mobile phase:  Acetonitrile, methanol, Solution C, and Solution D (300:200:4500:2)
System suitability solution:  0.2 mg/mL of USP Cefdinir RS and 0.5 mg/mL of USP Cefdinir Related Compound A RS in Buffer
Standard solution:  0.2 mg/mL of USP Cefdinir RS in Buffer
Sample solution:  0.2 mg/mL of Cefdinir in Buffer
Chromatographic system  
(See Chromatography 621, System Suitability.)
Mode:  LC
Detector:  UV 254 nm
Column:  4.6-mm × 15-cm; 5-µm packing L1
Column temperature:  40
Flow rate:  1 mL/min
Injection size:  5 µL
System suitability 
Samples:  System suitability solution and Standard solution. USP Cefdinir Related Compound A RS should produce four peaks.
Tailing factor:  NMT 1.5 for cefdinir, System suitability solution
Resolution:  NLT 1.2 between the second peak of cefdinir related compound A and cefdinir, System suitability solution
Relative standard deviation:  NMT 1.0%, Standard solution
Analysis 
Samples:  Standard solution and Sample solution
Calculate the quantity, in µg/mg, of cefdinir (C14H13N5O5S2) in the portion of Cefdinir taken:
Result = (rU/rS) × (CS/CU) × P
rU == peak response from the Sample solution
rS == peak response from the Standard solution
CS == concentration of the Standard solution (mg/mL)
CU == concentration of the Sample solution (mg/mL)
P== purity of USP Cefdinir RS (µg/mg)
Acceptance criteria:  940–1030 µg/mg on the anhydrous basis
IMPURITIES
•  Residue on Ignition 281: NMT 0.20%
Change to read:
•  Organic Impurities
Solution A, Solution B, Solution C, Solution D, and Buffer:  Prepare as directed in the Assay.
Solution E:  To 1000 mL of Solution C add 0.4 mL of Solution D.
Solution F:  Acetonitrile, methanol, Solution C, and Solution D (300: 200: 500: 0.4)
Mobile phase:  See Table 1.
Table 1
Time
(min)		 Solution E
(%)		 Solution F
(%)
0 95 5
2 95 5
22 75 25
32 50 50
37 50 50
38 95 5
58 95 5
System suitability solution 1:  15 µg/mL of cefdinir from the Sample solution, diluted with Solution C
System suitability solution 2:  1.5 µg/mL of cefdinir from System suitability solution 1, diluted with Solution C
System suitability solution 3:  1.5 mg/mL of USP Cefdinir RS and 0.1 mg/mL of USP Cefdinir Related Compound A RS, dissolved initially in Buffer corresponding to 15% of the final volume, and diluted with Solution C to volumeUSP35
Sample stock solution:  10 mg/mL of Cefdinir in Buffer
Sample solution:  1.5 mg/mL of cefdinir from the Sample stock solution, in Solution C. [Note—Prepare fresh immediately before use. ]
Chromatographic system  
(See Chromatography 621, System Suitability.)
Mode:  LC
Detector:  UV 254 nm
Column:  4.6-mm × 15-cm; 5-µm packing L1
Column temperature:  40
Flow rate:  1 mL/min
Injection size:  10 µL
System suitability 
Samples:  System suitability solution 1, System suitability solution 2, and System suitability solution 3. USP Cefdinir Related Compound A RS should produce four peaks. USP35
Suitability requirements 
Response ratio:  The response of cefdinir from System suitability solution 2 is between 7% and 13% of that from System suitability solution 1.
Resolution:  NLT 1.5 between cefdinir and the third peak of USP Cefdinir Related Compound A RS, System suitability solution 3USP35
Relative standard deviation:  NMT 2.0% for cefdinir, System suitability solution 3
Analysis 
Sample:  Sample solution. Record the chromatogram for at least 1.8 times the retention time of the cefdinir peak.USP35
Calculate the percentage of each impurity in the portion of Cefdinir taken:
Result = (rU/rT) × 100
rU== peak response of each impurity from the Sample solution
rT== sum of all the peak responses from the Sample solution
Acceptance criteria:  See Table 2.
Table 2
Name Relative
Retention
Time		 Acceptance
Criteria,
NMT (%)
Thiazolylacetyl glycine oximea 0.10 0.5
Thiazolylacetyl glycine oxime acetalb 0.12 0.5
3-Methyl cefdinirc 0.74 0.7
Cefdinir related compound A (cefdinir open ring lactone a)d,e 0.85 0.7
Cefdinir related compound A (cefdinir open ring lactone b)d,e 0.93
Cefdinir related compound A (cefdinir open ring lactone c)d,e 1.11
Cefdinir related compound A (cefdinir open ring lactone d)d,e 1.14
Cefdinir lactonef 1.22 0.5
Cefdinir isoxazole analogg 1.36 0.5
E-Cefdinirh 1.51 0.7
Cefdinir decarboxy open ring lactone ai,j 1.61 0.5
Cefdinir decarboxy open ring lactone bi,j 1.64
Any other individual, unidentified impurity — 0.2
Total impurities — 3.0
a  1N-[(Z)-2-(2-Aminothiazol-4-yl)-2-(hydroxyimino)acetyl]glycine.
b  (Z)-2-(2-Aminothiazol-4-yl)-N-(2,2-dihydroxyethyl)-2-(hydroxyimino)acetamide.
c  (6R,7R)-7-[(Z)-2-(2-Aminothiazol-4-yl)-2-(hydroxyimino)acetamido]-3-methyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid.
d  2(R)-2-[(Z)-2-(2-Aminothiazol-4-yl)-2-(hydroxyimino)acetamido)]-2-[(2RS,5RS)-5-methyl-7-oxo-2,4,5,7-tetrahydro-1H-furo[3,4-d][1,3]thiazin-2-yl]acetic acid.
e  Cefdinir related compound A is a mixture of 4 isomers labeled cefdinir open ring lactones a, b, c, and d. The sum of the values is reported. The limit for the sum of the 4 isomers is 0.7%.
f  (Z)-2-(2-Aminothiazol-4-yl)-2-(hydroxyimino)-N-{(3RS,5aR,6R)-3-methyl-1,7-dioxo-1,3,4,5a,6,7-hexahydroazeto[2,1-b]furo[3,4-d][1,3]thiazin-6-yl}acetamide.
g  (6R,7R)-7-(4-Hydroxyisoxazole-3-carboxamido)-8-oxo-3-vinyl-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid.
h  (6R,7R)-7-[(E)-2-(2-Aminothiazol-4-yl-)-2-(hydroxyimino)acetamido]-8-oxo-3-vinyl-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid.
i  (Z)-2-(2-Aminothiazol-4-yl)-2-(hydroxyimino)-N-{[(2RS,5RS)-5-methyl-7-oxo-2,4,5,7-tetrahydro-1H-furo[3,4-d][1,3]thiazin-2-yl]methyl}acetamide.
j  Cefdinir decarboxy open ring lactone is a mixture of 2 isomers labeled cefdinir decarboxy open ring lactones a and b. The sum of the values is reported. The limit for sum of the 2 isomers is 0.5%.
USP35
SPECIFIC TESTS
•  Optical Rotation, Specific Rotation 781S
Sample solution:  10 mg/mL in Buffer, as obtained in the Assay
Acceptance criteria:  61 to 67 at 20
•  Water Determination, Method I 921: NMT 2.0% for anhydrous; 4.0%–8.5% for hydrated forms. For this monograph, the term “hydrated forms” refers to several known forms of Cefdinir. Use a mixture of formamide and methanol (2:1) as the solvent.
ADDITIONAL REQUIREMENTS
•  Packaging and Storage: Preserve in tight, light-resistant containers.
•  USP Reference Standards 11
USP Cefdinir RS
USP Cefdinir Related Compound A RS Click to View Structure
(2R)-2-[(Z)-2-(2-Aminothiazol-4-yl)-2-(hydroxyimino)acetamido]-2-[(2RS,5RS)-5-methyl-7-oxo-2,4,5,7-tetrahydro-1H-furo[3,4-d][1,3]thiazin-2-yl]acetic acid (three other stereoisomers are also present in this RS).
    C14H15N5O6S2        413.43
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