Efavirenz Capsules
DEFINITION
Efavirenz Capsules contain NLT 92.0% and NMT 108.0% of the labeled amount of efavirenz (C14H9ClF3NO2).
IDENTIFICATION
• A. Infrared Absorption 197K
Sample solution:
Dissolve the contents of 1 Capsule in about 5 mL of acetonitrile by mixing on a vortex mixer. Allow to settle, remove about 3 mL of the solution, and centrifuge for about 5 min. Transfer 12 mL of supernatant to a clean suitable container, and evaporate to dryness under nitrogen. Mix 0.51 mg of the powder with 200 mg of potassium bromide.
• B. Ultraviolet Absorption 197U
Solvent:
Acetonitrile
Standard solution:
10 µg/mL in Solvent
Sample solution:
Dissolve the contents of 1 Capsule in about 40 mL of Solvent by shaking for about 30 min. Pass through a suitable nylon or PVDF membrane filter, discarding the first 2 mL of filtrate, and dilute a portion with acetonitrile to a concentration of 10 µg/mL of efavirenz.
Acceptance criteria:
The UV absorption spectrum of the Sample solution exhibits maxima and minima at the same wavelengths as does the Standard solution.
ASSAY
• Procedure
Diluent:
Acetonitrile and water (1:1)
Solution A:
Methanol, trifluoroacetic acid, and water (1:0.005:9). [NoteUse only freshly-opened trifluoroacetic acid, 6 months. ]
Solution B:
Methanol, trifluoroacetic acid, and water (9:0.005:1). [NoteUse only freshly-opened trifluoroacetic acid, 6 months. ]
Mobile phase:
See the gradient table below.
Standard solution 1:
0.2 mg/mL of USP Efavirenz Related Compound B RS in Diluent
Standard solution 2:
5 mg/mL of USP Efavirenz RS in acetonitrile. [NoteSonicate to dissolve before diluting to final volume. ]
Standard solution:
250 µg/mL of USP Efavirenz RS and 1 µg/mL of USP Efavirenz Related Compound B RS in Diluent prepared from Standard solution 2 and Standard solution 1, respectively. [NoteStore protected from light. For the HPLC analysis, it is recommended to use polypropylene vials, because degradation has been noted with certain brands made of glass. ]
Sample stock solution:
Transfer the contents of NLT 10 Capsules to a suitable container, and extract the contents in acetonitrile by mixing for about 30 min to obtain a quantitative solution equivalent to about 5 mg/mL of efavirenz. [NoteStore protected from light. ]
Sample solution:
Filter a portion of the Sample stock solution, and dilute the filtrate with Diluent to obtain a solution of about 250 µg/mL of efavirenz. [NoteStore protected from light. For the HPLC analysis, it is recommended to use polypropylene vials, because degradation has been noted with certain brands made of glass. ]
Chromatographic system
Mode:
LC
Detector:
UV 250 nm
Column:
4.6-mm × 15-cm; packing L10
Column temperature:
40
Flow rate:
1.5 mL/min
Injection size:
35 µL
System suitability
Sample:
Standard solution
Suitability requirements
Resolution:
NLT 1.2 between efavirenz related compound B and efavirenz
Relative standard deviation:
NMT 2.0% for efavirenz
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of efavirenz (C14H9ClF3NO2) in the portion of Capsules taken:
Result = (rU/rS) × (CS/CU) × 100
Acceptance criteria:
92.0%108.0%
PERFORMANCE TESTS
• Dissolution 711
Medium:
1.0% (w/v) sodium lauryl sulfate in water; 900 mL. [NoteDo not deaerate. ]
Apparatus 2:
50 rpm, with helix sinker
Time:
45 min
Standard solution:
(L/900) mg/mL of USP Efavirenz RS in Medium, where L is the Capsule label claim in mg. A small volume of methanol, NMT 10% of the final volume, could be used to solubilize efavirenz. Dilute this solution with Medium to obtain a final concentration of about 0.01 mg/mL for Capsules labeled to contain 50 mg, or about 0.02 mg/mL for Capsules labeled to contain 100 mg or 200 mg.
Sample solution:
Pass a portion of the solution under test through a suitable filter of 0.45-µm pore size, and dilute with Medium to obtain a theoretical concentration similar to the Standard solution, assuming complete dissolution of the Capsule label claim.
Analytical wavelength:
UV 247 nm
Cell:
1 cm
Blank:
Medium
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of efavirenz dissolved:
Result = (AU/AS) × (CS/L) × D × V × 100
Tolerances:
NLT 80% (Q) of the labeled amount of efavirenz is dissolved.
• Uniformity of Dosage Units 905:
Meet the requirements
Procedure for content uniformity
Standard solution:
10 µg/mL of USP Efavirenz RS in acetonitrile
Sample solution:
Transfer the contents of 1 Capsule into a suitable container, and dissolve in 40.0 mL of acetonitrile. Shake for about 30 min and pass through a suitable nylon or PVDF membrane filter. Dilute a portion of the filtrate to an efavirenz concentration of about 10 µg/mL.
Spectrometric conditions
Mode:
UV absorption spectroscopy
Analytical wavelength:
UV 246 nm
Cell:
1 cm
Blank:
Acetonitrile
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of efavirenz (C14H9ClF3NO2) in the portion of Capsules taken:
Result = (AU/AS) × (CS/L) × V × D × 100
IMPURITIES
Organic Impurities
• Procedure
Diluent, Solution A, Solution B, Sample solution, and Chromatographic system:
Prepare as directed in the Assay.
System suitability solution:
Use the Standard solution prepared as directed in the Assay.
Standard solution:
1.25 µg/mL of USP Efavirenz RS and 0.005 µg/mL of USP Efavirenz Related Compound B RS in Diluent from the System suitability solution
System suitability
Samples:
System suitability solution and Standard solution
Suitability requirements
Resolution:
NLT 1.2 between efavirenz related compound B and efavirenz, System suitability solution
Relative standard deviation:
NMT 5.0% for efavirenz, Standard solution
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of any individual impurity in the portion of Capsules taken:
Result = (rU/rS) × (CS/CU) × (1/F) × 100
Acceptance criteria
Individual impurities:
See Impurity Table 1. [NoteDisregard any peak less than 0.05%. ]
Total impurities:
NMT 0.50%. [NoteInclude only the degradation products in the calculation of the total impurities. ]
Impurity Table 1
ADDITIONAL REQUIREMENTS
• Packaging and Storage:
Store in well-closed containers at controlled room temperature.
• USP Reference Standards 11
USP Efavirenz Related Compound B RS
(S,E)-6-Chloro-4-(2-cyclopropylvinyl)-4-(trifluoromethyl)-2H-3,1-benzoxazin-2-one. C14H11ClF3NO2 317.69
Auxiliary Information
Please check for your question in the FAQs before contacting USP.
USP35NF30 Page 3013
Pharmacopeial Forum: Volume No. 36(3) Page 664
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