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Printed by: USP NF Official Date: Official as of 01-Jan-2018 Document Type: USP @2024 USPC
Do Not Distribute DOI Ref: 2fk70 DOI: https://doi.org/10.31003/USPNF_M40428_04_01
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Detector: 240 nm. For Identification C, use a diode array
Indomethacin Sodium detector in the range of 190–400 nm.
Column: 4.6-mm × 25-cm; 5-µm packing L1
Column temperature: 40°
Flow rate: 1 mL/min
Injection volume: 10 µL
System suitability
Samples: System suitability solution and Standard solution
[NOTE—The relative retention times for indomethacin
C19H15ClNNaO4 · 3H2O 433.82 related compound A and indomethacin related
1H-Indole-3-acetic acid, 1-(4-chlorobenzoyl)-5-methoxy-2- compound B are 0.50 and 0.67, respectively.]
methyl-, sodium salt, trihydrate; Suitability requirements
Sodium 1-(p-chlorobenzoyl)-5-methoxy-2-methylindole-3- Resolution: NLT 10 between indomethacin related
acetate, trihydrate CAS RN®: 74252-25-8; UNII: compound A and indomethacin related compound B,
0IMX38M2GG. System suitability solution
Anhydrous 379.78 Tailing factor: NMT 2.0 for indomethacin, Standard
solution
DEFINITION Relative standard deviation: NMT 0.73%, Standard
Indomethacin Sodium contains NLT 98.0% and NMT 102.0% solution
of indomethacin sodium (C19H15ClNNaO4), calculated on the Analysis
dried basis. Samples: Standard solution and Sample solution
Calculate the percentage of indomethacin sodium
IDENTIFICATION
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(C19H15ClNNaO4) in the portion of Indomethacin
• A.
Sample: A small quantity Sodium taken:
Analysis: Ignite the Sample on a platinum wire in a Result = (r U/r S) × (C S/C U) × (M r1/M r2) × 100
nonluminous flame.
Acceptance criteria: An intense yellow flame is produced. ci rU = peak response from the Sample solution
• B. The retention time of the major peak of the Sample rS = peak response from the Standard solution
solution corresponds to that of the Standard solution, as
obtained in the Assay. CS = concentration of USP Indomethacin RS in the
• C. The UV-Vis spectrum of the major peak of the Sample Standard solution (mg/mL)
solution corresponds to that of the Standard solution, as CU = concentration of Indomethacin Sodium in the
Sample solution (mg/mL)
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obtained in the Assay.
M r1 = molecular weight of anhydrous indomethacin
ASSAY sodium, 379.78
• PROCEDURE M r2 = molecular weight of indomethacin, 357.79
Solution A: 0.1% formic acid in water
Solution B: 0.025% formic acid in acetonitrile Acceptance criteria: 98.0%–102.0% on the dried basis
Mobile phase: See Table 1.
O
IMPURITIES
Table 1 • LIMIT OF ACETONE
Standard solution: Transfer 1.0 mL of acetone to a 100-mL
Time Solution A Solution B volumetric flask, and dilute with water to volume. Transfer
(min) (%) (%)
1.0 mL of this solution to a 200-mL volumetric flask, dilute
0 70 30 with water to volume, insert a stopper, and cool in an
2 70 30
ice bath.
Sample solution: Transfer 100 mg of Indomethacin Sodium
20 15 85 to a 15-mL centrifuge tube, and dissolve in 1.0 mL of cool
25 15 85 water. While vortexing this solution, add 1.0 mL of 0.24 N
hydrochloric acid, centrifuge promptly, and filter the
26 70 30 supernatant. Collect the filtrate in a suitable tube, cap, and
30 70 30 cool in an ice bath.
Chromatographic system
(See Chromatography á621ñ, System Suitability.)
Diluent: Solution B and Solution A (45:55) adjusted with Mode: GC
0.2 M sodium hydroxide to a pH of 8.0 Detector: Flame ionization
System suitability solution: 0.82 mg/mL of USP Column: 3-mm × 1.8-m; support S3
Indomethacin RS, 0.002 mg/mL of USP Indomethacin Column temperature: 165°
Related Compound A RS, and 0.002 mg/mL of USP Carrier gas: Nitrogen
Indomethacin Related Compound B RS in Diluent. Sonicate Injection volume: 3 µL
to dissolve. System suitability
Standard solution: 0.82 mg/mL of USP Indomethacin RS Sample: Standard solution
dissolved in a minimum quantity of acetonitrile. Dilute with Suitability requirements
Diluent to volume. Sonicate to dissolve. Capacity factor, k ′: 4–7 for acetone
Sample solution: 1.0 mg/mL of Indomethacin Sodium Relative standard deviation: NMT 2.0%
trihydrate in Diluent. Sonicate to dissolve. Analysis
Chromatographic system Samples: Standard solution and Sample solution
(See Chromatography á621ñ, System Suitability.)
Mode: LC
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Printed on: Fri Jan 05 2024, 09:31:14 PM(EST) Status: Currently Official on 06-Jan-2024 DocId: GUID-FCC5C655-1AAD-4BA7-8BD4-9E354B03CED8_4_en-US
Printed by: USP NF Official Date: Official as of 01-Jan-2018 Document Type: USP @2024 USPC
Do Not Distribute DOI Ref: 2fk70 DOI: https://doi.org/10.31003/USPNF_M40428_04_01
2
[NOTE—Use the solvent flush technique, with water as rU = peak response of any individual unspecified
the flushing agent, and record the chromatograms impurity from the Sample solution
for 6 min.] rS = peak response of indomethacin from the Standard
Calculate the percentage of acetone in the portion of solution
Indomethacin Sodium taken: CS = concentration of USP Indomethacin RS in the
Standard solution (mg/mL)
Result = S G (10/W U)(r U/r S) CU = concentration of Indomethacin Sodium in the
Sample solution (mg/mL)
SG = specific gravity of acetone, 0.79
WU = quantity of Indomethacin Sodium taken to Acceptance criteria: See Table 2.
prepare the Sample solution (mg)
rU = peak area of acetone from the Sample solution Table 2
rS = peak area of acetone from the Standard solution Relative Acceptance
Retention Criteria,
Acceptance criteria: NMT 0.1% Name Time NMT (%)
• ORGANIC IMPURITIES Indomethacin related compound A 0.50 0.2a
Solution A, Solution B, Mobile phase, Diluent, and
Chromatographic system: Proceed as directed in the Indomethacin related compound B 0.67 —
Assay. Indomethacin 1.0 —
Standard solution: 0.002 mg/mL each of USP
Any individual unspecified impurity — 0.5
Indomethacin RS, USP Indomethacin Related Compound A
RS, and USP Indomethacin Related Compound B RS, Total impurities — 1.0b
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dissolved in a minimum quantity of acetonitrile. Dilute with
Diluent to volume. Sonicate to dissolve. a The sum of the percentages of indomethacin related compound A and
Sample solution: 1.0 mg/mL of Indomethacin Sodium in indomethacin related compound B is NMT 0.2%.
b Excluding the percentages for indomethacin related compound A and
Diluent. Sonicate to dissolve. indomethacin related compound B.
System suitability
Sample: Standard solution
Suitability requirements
Resolution: NLT 10 between indomethacin related
compound A and indomethacin related compound B
ci SPECIFIC TESTS
• LOSS ON DRYING á731ñ
Analysis: Dry at 100° for 2 h at a pressure not exceeding
5 mm of mercury.
Relative standard deviation: NMT 2.5% for Acceptance criteria: 11.5%–13.5%
indomethacin related compound A, indomethacin • OTHER REQUIREMENTS: Where the label states that
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related compound B, and indomethacin Indomethacin Sodium is sterile, it meets the requirements
Analysis for Sterility Tests á71ñ and for the Bacterial Endotoxins Test
Samples: Standard solution and Sample solution under Indomethacin for Injection. Where the label states that
Calculate the percentage of indomethacin related Indomethacin Sodium must be subjected to further
compound A or indomethacin related compound B in the processing during the preparation of injectable dosage
portion of Indomethacin Sodium taken:
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forms, it meets the requirements for the Bacterial
Result = (r U/r S) × (C S/C U) × 100 Endotoxins Test under Indomethacin for Injection.
ADDITIONAL REQUIREMENTS
rU = peak response of indomethacin related • PACKAGING AND STORAGE: Preserve in well-closed,
compound A or indomethacin related light-resistant containers.
compound B from the Sample solution • LABELING: Where it is intended for use in preparing
rS = peak response of the corresponding related injectable dosage forms, the label states that it is sterile or
compound from the Standard solution must be subjected to further processing during the
CS = concentration of the corresponding USP preparation of injectable dosage forms.
Reference Standard in the Standard solution (mg/ • USP REFERENCE STANDARDS á11ñ
mL) USP Indomethacin RS
CU = concentration of Indomethacin Sodium in the USP Indomethacin Related Compound A RS
Sample solution (mg/mL) 2-(5-Methoxy-2-methyl-1H-indol-3-yl)acetic acid.
(C12H13NO3) 219.24
Calculate the percentage of any individual unspecified USP Indomethacin Related Compound B RS
impurity in the portion of Indomethacin Sodium taken: 4-Chlorobenzoic acid.
(C7H5ClO2) 156.57
Result = (r U/r S) × (C S/C U) × 100
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