Cefdinir Capsules
DEFINITION
Cefdinir Capsules contain NLT 90.0% and NMT 110.0% of the labeled amount of cefdinir (C14H13N5O5S2).
IDENTIFICATION
•  A. Ultraviolet Absorption 197U
Buffer:  Prepare as directed in the Assay.
Blank:  Use the Buffer.
Standard solution:  10 µg/mL of USP Cefdinir RS in Buffer
Sample solution:  Equivalent to 10 µg/mL of cefdinir from Capsules in Buffer. Filter before use.
Cell size:  1 cm
Acceptance criteria:  Sample solution maxima and minima occur at the same wavelengths as those in the Standard solution.
•  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
Buffer:  10.7 g/L of dibasic sodium phosphate and 3.4 g/L of monobasic potassium phosphate. Adjust with phosphoric acid or sodium hydroxide to a pH of 7.0 ± 0.05 before final dilution.
Solution A:  7 g/L citric acid monohydrate. Adjust with phosphoric acid to a pH of 2.0 ± 0.05.
Mobile phase:  Methanol, tetrahydrofuran, and Solution A (111:28:1000)
System suitability solution:  50 µg/mL of USP Cefdinir RS and 175 µg/mL of m-hydroxybenzoic acid in Buffer
Standard solution:  50 µg/mL of USP Cefdinir RS in Buffer
Sample solution:  Equivalent to 50 µg/mL of cefdinir, from Capsule contents (NLT 20) in Buffer
Chromatographic system 
(See Chromatography 621, System Suitability.)
Mode:  LC
Detector:  UV 254 nm
Column:  3.9-mm × 15-cm; 4-µm packing L1
Flow rate:  1.4 mL/min
Injection size:  15 µL
System suitability 
Samples:  System suitability solution and Standard solution
Suitability requirements 
Resolution:  Greater than 3.0 between cefdinir and m-hydroxybenzoic acid, System suitability solution
Tailing factor:  NMT 2.0 for cefdinir, System suitability solution
Relative standard deviation:  NMT 1.0% for cefdinir, Standard solution
Analysis 
Samples:  Standard solution and Sample solution
Calculate the percentage of the labeled amount of cefdinir (C14H13N5O5S2) in the portion of Capsules taken:
Result = (rU/rS) × (CS/CU) × 100
rU== peak response for cefdinir from the Sample solution
rS== peak response for cefdinir from the Standard solution
CS== concentration of the Standard solution (µg/mL)
CU== nominal concentration of cefdinir in the Sample solution (µg/mL)
Acceptance criteria:  90.0%–100.0%
PERFORMANCE TESTS
•  Dissolution 711
Medium:  50 mM phosphate buffer pH 6.8; 900 mL
Apparatus 2:  50 rpm
Time:  30 min
Detector:  UV 290 nm
Cell length:  0.1-cm flow cell
Standard solution:  0.33 mg/mL of USP Cefdinir RS in Medium
Sample solution:  Pass a portion of the solution under test through a suitable filter of 0.45-µm pore size. Dilute with Medium to a concentration of about 0.33 mg/mL of cefdinir.
Blank:  Dissolve 1 empty Capsule in 100 mL of Medium, and dilute to 900 mL. Filter if necessary.
Analysis:  Determine the percentage of the labeled amount of cefdinir (C14H13N5O5S2) dissolved:
Result = (AU/AS) × CS × D × (V/L) × 100
AU== absorbance of the Sample solution
AS== absorbance of the Standard solution
CS== concentration of the Standard solution (mg/mL)
D== dilution factor of the Sample solution (mL/mL)
V== volume of Medium, 900 mL
L== label claim (mg/Capsule)
Tolerances:  NLT 80% (Q) of the labeled amount of cefdinir (C14H13N5O5S2) is dissolved.
•  Uniformity of Dosage Units 905: Meet the requirements
IMPURITIES
Change to read:
•  Organic Impurities
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% aqueous) with water to obtain a 0.1% solution. Adjust with dilute phosphoric acid (1 in 10) to a pH of 5.5 ± 0.1.
Solution D:  37.2 mg/mL of edetate disodium
Solution E:  To 1000 mL of Solution C add 0.4 mL of Solution D.
Solution F:  Acetonitrile, methanol, Solution C, and Solution D (150: 100: 250: 0.2)
Buffer:  Combine appropriate amounts of Solution A and Solution B (about 2:1) to obtain a solution with a pH of 7.0 ± 0.1.
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 stock solution 1:  40 µg/mL of USP Cefdinir Related Compound A RS in Solution C
System suitability stock solution 2:  40 µg/mL of USP Cefdinir Related Compound B RS in Solution C
System suitability solution:  Transfer 37.5 mg of USP Cefdinir RS to a 25-mL volumetric flask. Add about 10 mL of Buffer. Add 5.0 mL of each of System suitability stock solution 1 and System suitability stock solution 2, and dilute with Solution C to volume.
Standard stock solution:  750 µg/mL of USP Cefdinir RS in Buffer
Standard solution:  15 µg/mL of USP Cefdinir RS, from the Standard stock solution in Solution C
Sample solution:  Transfer an equivalent to 300 mg of cefdinir from Capsule contents (NLT 20) into a 200-mL volumetric flask. Dissolve in 30 mL of Buffer, and dilute with Solution C to volume to obtain a solution having a nominal concentration of about 1.5 mg/mL of cefdinir.
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
Autosampler temperature:  4
Flow rate:  1 mL/min
Injection size:  10 µL
System suitability 
Samples:  System suitability solution and Standard solution
Suitability requirements 
Resolution:  NLT 1.5 between cefdinir and the third peak of the USP Cefdinir Related Compound A RS, System suitability solution
Tailing factor:  NMT 1.5 for cefdinir related compound B, System suitability solution
Relative standard deviation:  NMT 2.0% for the cefdinir peak response, Standard solution
Analysis 
Samples:  Standard solution and Sample solution
Calculate the percentage of each impurity in the portion of Capsules taken:
Result = (rU/rS) × (CS/CU) × (100/F)
rU== peak response of each impurity 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)
F== relative response factor (see Table 2)
Acceptance criteria:  See Table 2.
Table 2
Name Relative
Retention
Time		 Relative
Response
Factor 		Reporting
Threshold
(% Cefdinir) 		Acceptance
Criteria,
NMT (%)
Thiazolylacetyl glycine oximea 0.10 1.1 0.1 0.5
Thiazolylacetyl glycine oxime acetalb 0.13 1.1 0.1 0.5
Cefdinir sulfoxidec 0.36 1.0 0.05 0.2
Cefdinir thiazine analogd 0.46 1.5 0.05 0.7
3-Methyl cefdinire 0.75 1.0 0.05 0.7
Cefdinir impurity 1f 0.77 1.0 0.05 0.3
Cefdinir related compound A (cefdinir open ring lactone a)g,h 0.85 1.5 0.1 2.5
Cefdinir related compound A (cefdinir open ring lactone b)g,h 0.94 1.5 0.1
Cefdinir related compound A (cefdinir open ring lactone c)g,h 1.11 1.5 0.1
Cefdinir related compound A (cefdinir open ring lactone d)g,h 1.14 1.5 0.1
7S-Cefdiniri 1.18 1.1 0.05 0.2
Cefdinir lactonej 1.23 1.2 0.05 1.0
Cefdinir related compound Bk 1.28 1.1 0.05 0.2
Cefdinir isoxazole analogl 1.37 1.4 0.05 0.5
Cefdinir impurity 2e 1.44 1.0 0.05 0.5
Cefdinir glyoxalic analogm 1.49 1.0 0.05 0.2
E-cefdinirn 1.51 1.1 0.05 0.7
Cefdinir decarboxy open ring lactone ao,p 1.62 1.3 0.05 1.0
Cefdinir decarboxy open ring lactone bo,p 1.64 1.3 0.05
Cefdinir impurity 3e 1.82 1.0 0.05 0.2
Individual unidentified impurities — 1.0 0.05 0.2
Total impurities — — — 5.0
a  N-[(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]-5,8-dioxo-3-vinyl-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid.
d  (R,Z)-2-{(R)-[(Z)-2-(2-Aminothiazol-4-yl)-2-(hydroxyimino)acetamido](carboxy)methyl}-5-ethylidene-5,6-dihydro-2H-1,3-thiazine-4-carboxylic acid.
e  (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.
f  Cefdinir impurity 1, cefdinir impurity 2, and cefdinir impurity 3 are unidentified impurities.
g  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 2.5%.
h  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.
i  (6R,7S)-7-[(Z)-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.
j  (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.
k  (6R,7R)-7-[2-(2-Amino-4-thiazolyl)acetamido]-8-oxo-3-vinyl-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid.
l  (6R,7R)-7-(4-Hydroxyisoxazole-3-carboxamido)-8-oxo-3-vinyl-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid.
m  (6R,7R)-7-[2-(2-Aminothiazol-4-yl)-2-oxoacetamido]-8-oxo-3-vinyl-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid.
n  (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.
o  Cefdinir decarboxy open ring lactone is a mixture of 2 isomers labeled cefdinir decarboxy open ring lactone a and b. The sum of the values is reported. The limit for sum of the 2 isomers is 1.0%.
p  (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.
USP35
ADDITIONAL REQUIREMENTS
•  Packaging and Storage: Preserve in tight light-resistant containers, and store at controlled room temperature.
•  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
USP Cefdinir Related Compound B RS Click to View Structure
(6R,7R)-7-[2-(2-Amino-4-thiazolyl)acetamido]-8-oxo-3-vinyl-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid.
    C14H13N4O4S2        365.41
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