Authorized USP Pending Monograph
Version 1
Etonogestrel / 1
BRIEFING
Etonogestrel. This USP Pending Monograph was posted on
the USP website as Draft 1 on April 26, 2013. No comments
were received. The Monographs—Small Molecules 4 Expert
Committee has approved the monograph as an Authorized
USP Pending Monograph.
The liquid chromatographic procedure in the Assay and the
test for Organic Impurities was validated with the Synergy
Hydro RP-80Å brand of L1 column. The typical retention
time for etonogestrel is about 26 min.
Additionally, minor editorial changes have been made to update the monograph to current USP style.
Description and Solubility: White to almost white, crystalline
powder. Freely soluble in methanol and in dichloromethane; soluble in acetone; practically insoluble in water.
(SM4: D. Vicchio.) Correspondence Number—C113308
Sample solution: 0.5 mg/mL of Etonogestrel in
acetonitrile
Chromatographic system
(See Chromatography 〈621〉, System Suitability.)
Mode: LC
Detector: UV 240 nm
Column: 4.6-mm × 15-cm; 4-µm packing L1
Column temperature: 40°
Flow rate: 1 mL/min
Injection volume: 20 µL
System suitability
Sample: Standard solution
[NOTE—The relative retention times for etonogestrel related compound A and etonogestrel are 0.96 and 1.0,
respectively.]
Suitability requirements
Resolution: NLT 1.2 between etonogestrel related
compound A and etonogestrel
Relative standard deviation: NMT 0.73% for
etonogestrel
Analysis
Samples: Standard solution and Sample solution
Calculate the percentage of etonogestrel (C22H28O2) in
the portion of Etonogestrel taken:
Etonogestrel
.
Result = (rU/rS) × (CS/CU) × 100
v.1 Authorized January 1, 2014
rU
C22H28O2
324.46
18,19-Dinor-17α-pregn-4-en-20-yn-3-one, 13-ethyl-17-hydroxy-11-methylene;
13-Ethyl-17-hydroxy-11-methylene-18,19-dinor-17α-pregn4-en-20-yn-3-one [54048-10-1].
DEFINITION
Etonogestrel contains NLT 98.0% and NMT 102.0% of the
labeled amount of etonogestrel (C22H28O2), calculated on
the dried basis.
IDENTIFICATION
• A. INFRARED ABSORPTION 〈197A〉
Sample: Potassium bromide dispersion containing 5%
Etonogestrel
Acceptance criteria: Meets the requirements
• 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: Acetonitrile
Solution B: Water
Mobile phase: See Table 1.
= peak response of etonogestrel from the
Sample solution
rS
= peak response of etonogestrel from the
Standard solution
CS
= concentration of USP Etonogestrel RS in the
Standard solution (mg/mL)
CU
= concentration of Etonogestrel in the Sample
solution (mg/mL)
Acceptance criteria: 98.0%–102.0% on the dried basis
IMPURITIES
• HEAVY METALS, Method I 〈231〉: NMT 20 ppm
• RESIDUE ON IGNITION 〈281〉: NMT 0.2%
• ORGANIC IMPURITIES
Mobile phase, Standard solution, Sample solution, and
Chromatographic system: Proceed as directed in the
Assay.
Sensitivity solution: 0.1 µg/mL of USP Etonogestrel RS in
acetonitrile from the Standard solution
System suitability
Samples: Standard solution and Sensitivity solution
[NOTE—The relative retention times for etonogestrel related compound A and etonogestrel are 0.96 and 1.0,
respectively.]
Suitability requirements
Resolution: NLT 1.2 between etonogestrel related
compound A and etonogestrel, Standard solution
Signal-to-noise ratio: NLT 10 for etonogestrel, Sensitivity solution
Analysis
Sample: Sample solution
Calculate the percentage of each impurity in the portion
of Etonogestrel taken:
Result = (rU/rT) × 100
Table 1
Time
(min)
0
35
40
50
Solution A
(%)
35
50
35
35
rU
Solution B
(%)
65
50
65
65
= peak area for each impurity from the Sample
solution
rT
= total peak area from the Sample solution
Acceptance criteria
Individual impurities: NMT 0.10%
Total impurities: NMT 0.3%
Disregard any impurity peak less than 0.02%.
Standard solution: 0.5 mg/mL of USP Etonogestrel RS
and 0.025 mg/mL of USP Related Compound A RS in
acetonitrile
This monograph has been developed under USP‘s Pending Monographs Guideline and is not a USP–NF monograph.
http://www.usp.org
2013 The United States Pharmacopeia. All Rights Reserved.
2 / Etonogestrel
SPECIFIC TESTS
• LOSS ON DRYING 〈731〉
Sample: 1.0 g
Analysis: Dry the Sample at 105° for NLT 30 min.
Acceptance criteria: NMT 1.0%
• OPTICAL ROTATION, Specific Rotation 〈781S〉
Sample solution: 10 mg/mL in dichloromethane
Acceptance criteria: +85.0° to +95.0° on the dried basis
Authorized USP Pending Monograph
Version 1
• USP REFERENCE STANDARDS 〈11〉
USP Etonogestrel RS
USP Etonogestrel Related Compound A RS
13β-Ethyl-11-methylenegon-4-ene-3,17-dione.
C20H26O2 298.42
ADDITIONAL REQUIREMENTS
• PACKAGING AND STORAGE: Preserve in tight containers, and
store at room temperature.
This monograph has been developed under USP‘s Pending Monographs Guideline and is not a USP–NF monograph.
http://www.usp.org
2013 The United States Pharmacopeia. All Rights Reserved.