Etomidate Injection
DEFINITION
Etomidate Injection is a sterile, nonpyrogenic solution. It contains NLT 90.0% and NMT 110.0% of the labeled amount of etomidate (C14H16N2O2). It may contain suitable buffers and preservatives.
IDENTIFICATION
• A. Ultraviolet Absorption 197U
Sample solution:
10 µg/mL of etomidate in isopropyl alcohol
Medium:
Isopropyl alcohol
• 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:
0.7 g/L of monobasic sodium phosphate in water
Mobile phase:
Acetonitrile and Buffer (2:3)
Standard solution:
0.16 mg/mL of USP Etomidate RS in acetonitrile
Sample solution:
0.16 mg/mL of etomidate, from the Injection, in acetonitrile
Chromatographic system
Mode:
LC
Detector:
UV 254 nm
Column:
3.9-mm × 30-cm; packing L1
Flow rate:
2.3 mL/min
Injection size:
20 µL
System suitability
Sample:
Standard solution
Suitability requirements
Tailing factor:
NMT 2.0
Relative standard deviation:
NMT 2.0%
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of C14H16N2O2 in the portion of Injection taken:
Result = (rU/rS) × (CS/CU) × 100
Acceptance criteria:
90.0%110.0%
IMPURITIES
Organic Impurities
• Procedure 1: Related Compounds
Solution A:
Dissolve 6 g of sodium citrate dihydrate and 4 g of anhydrous citric acid in 1 L of water.
Solution B:
Acetonitrile
Mobile phase:
See the gradient table below.
Diluent:
Weigh 6 g of sodium citrate dihydrate and 4 g of anhydrous citric acid into a 1000-mL volumetric flask. Add 500 mL of water, and shake to dissolve. Add 110 mL of acetonitrile and 50 mL of methanol, and dilute with water to volume.
Standard stock solution:
0.1 mg/mL of USP Metomidate Hydrochloride RS in methanol
Standard solution:
4 µg/mL of USP Metomidate Hydrochloride RS in Diluent, from the Standard stock solution
Sensitivity solution:
0.8 µg/mL of USP Metomidate Hydrochloride RS in Diluent, from the Standard solution
System suitability solution:
0.02 mg/mL of USP Etomidate RS and 0.02 mg/mL of USP Metomidate Hydrochloride RS in Diluent
Sample solution:
0.8 mg/mL of etomidate, from the Injection, in Diluent
Chromatographic system
Mode:
LC
Detector:
UV 254 nm
Column:
3.9-mm × 30-cm; packing L1
Flow rate:
2.0 mL/min
Injection size:
50 µL
System suitability
Samples:
Standard solution, Sensitivity solution, and System suitability solution
Suitability requirements
Resolution:
NLT 2.0 between etomidate and metomidate, System suitability solution
Signal-to-noise ratio:
NLT 10, Sensitivity solution
Relative standard deviation:
NMT 3.0%, Standard solution
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of each impurity in the portion of Injection taken:
Result = (rU/rS) × (CS/CU) × (Mr1/Mr2) × 100
Acceptance criteria
Individual impurities:
See Impurity Table 1. [NoteDisregard any impurity peaks less than 0.05%. ]
Total impurities:
NMT 1.6%
Impurity Table 1
• Procedure 2: Total Propylene Glycol Ester:
[NotePerform this test if propylene glycol is used in the formulation. ]
Mobile phase and Chromatographic system:
Proceed as directed in the Assay.
Standard solution:
25 µg/mL of USP Etomidate RS in acetonitrile
Sensitivity solution:
1.6 µg/mL of USP Etomidate RS in acetonitrile
Sample solution:
1.6 mg/mL of etomidate, from the Injection, in acetonitrile
System suitability
Samples:
Standard solution and Sensitivity solution
Suitability requirements
Tailing factor:
NMT 2.0, Standard solution
Signal-to-noise ratio:
NLT 10, Sensitivity solution
Relative standard deviation:
NMT 3.0%, Standard solution
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of each impurity in the portion of Injection taken:
Result = (rU/rS) × (CS/CU) × (1/F) × 100
Acceptance criteria
Individual impurities:
See Impurity Table 2. [NoteDisregard any impurity peaks less than 0.05%. ]
Total impurities:
NMT 4.0%. [NoteTotal impurities include all impurities from Impurity Table 1 and Impurity Table 2. ]
Impurity Table 2
SPECIFIC TESTS
• Bacterial Endotoxins Test 85:
It contains NMT 8.35 USP Endotoxin Units/mg of etomidate.
• Sterility Tests 71:
It meets the requirements when tested as directed for Test for Sterility of the Product to Be Examined, Membrane Filtration.
• pH 791:
Between 4.0 and 7.0
• Particulate Matter in Injections 788:
It meets the requirements for small-volume injections.
• Other Requirements:
It meets the requirements under Injections 1.
ADDITIONAL REQUIREMENTS
• Packaging and Storage:
Preserve in single-dose containers. Store at controlled room temperature.
• USP Reference Standards 11
USP Endotoxin RS
USP Metomidate Hydrochloride RS
Methyl 1-(1-phenylethyl)-1H-imidazole-5-carboxylate hydrochloride. C13H14N2O2· HCl 266.72
Auxiliary Information
Please check for your question in the FAQs before contacting USP.
USP35NF30 Page 3144
Pharmacopeial Forum: Volume No. 36(4) Page 919
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