Norelgestromin

This article is compiled based on the United States Pharmacopeia (USP) – 2025 Edition

Issued and maintained by the United States Pharmacopeial Convention (USP)

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C₂₁H₂₉NO₂ 327.46

18,19-Dinorpregn-4-en-20-yn-3-one, 13-ethyl-17-hydroxy-, oxime, (17α)-;

13-Ethyl-17-hydroxy-18,19-dinor-17α-pregn-4-en-20-yn-3-one oxime  CAS RN®: 53016-31-2; UNII: R0TAY3X631.

1 DEFINITION

Norelgestromin is a mixture of (E)- and (Z)-isomers having a ratio of (E)- to (Z)-isomer between 1.3 and 1.6, and the sum of both isomers is NLT 98.0% and NMT 102.0% of norelgestromin (C₂₁H₂₉NO₂), calculated on the anhydrous basis.

2 IDENTIFICATION

Change to read:

A. Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 〈197K〉

B. The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

3 ASSAY

3.1 Procedure

Mobile phase: Cyclohexane and absolute alcohol (100:2)

Diluent: Cyclohexane and absolute alcohol (90:10)

System suitability solution: 1.5 mg/mL of USP Norelgestromin RS and 8 µg/mL of USP Norelgestromin Related Compound A RS in Diluent

Standard solution: 1.5 mg/mL of USP Norelgestromin RS in Diluent

Sample solution: 1.5 mg/mL of Norelgestromin in Diluent

Chromatographic system

• (See Chromatography 〈621〉, System Suitability.)
• Mode: LC
• Detector: UV 210 nm
• Column: 4.6-mm × 25-cm; 5-µm packing L20
• Column temperature: 50°
• Flow rate: 1.2 mL/min
• Injection volume: 25 µL
• Run time: NLT 1.6 times the retention time of (Z)-norelgestromin

System suitability

• Samples: System suitability solution and Standard solution
• [Note-The relative retention times for the (Z)-isomer of norelgestromin related compound A, (E)-norelgestromin, and (Z)-norelgestromin are about 0.77, 0.85, and 1.0, respectively.]
• Suitability requirements
• Resolution: NLT 1.4 between the (Z)-isomer of norelgestromin related compound A and (E)-norelgestromin, System suitability solution
• Tailing factor: 0.8–1.2 for both (E)- and (Z)-norelgestromin, Standard solution
• Relative standard deviation: NMT 0.73% for both (E)- and (Z)-norelgestromin, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of norelgestromin (C₂₁H₂₉NO₂) in the portion of Norelgestromin taken:

Result = {[(r_ᵁᴱ × F) + r_ᵁᶻ]/[(r_ˢᴱ × F) + r_ˢᶻ]} × (C_ˢ/C_ᵁ) × 100

r_ᵁᴱ = peak response of (E)-norelgestromin from the Sample solution

F = response factor for (E)-norelgestromin, 1.04

r_ᵁᶻ = peak response of (Z)-norelgestromin from the Sample solution

r_ˢᴱ = peak response of (E)-norelgestromin from the Standard solution

r_ˢᶻ = peak response of (Z)-norelgestromin from the Standard solution

C_ˢ = concentration of USP Norelgestromin RS in the Standard solution (mg/mL)

C_ᵁ = concentration of Norelgestromin in the Sample solution (mg/mL)

Calculate the ratio of (E)- to (Z)-norelgestromin:

Result = (r_ᵁᴱ × F)/r_ᵁᶻ

r_ᵁᴱ = peak response of (E)-norelgestromin from the Sample solution

F = response factor for (E)-norelgestromin, 1.04

r_ᵁᶻ = peak response of (Z)-norelgestromin from the Sample solution

Acceptance criteria

• Both isomers: 98.0%–102.0% on the anhydrous basis
• Ratio of (E)- to (Z)-isomer: 1.3–1.6

4 IMPURITIES

4.1 Residue on Ignition 〈281〉: NMT 0.2%

4.2 Organic Impurities

Mobile phase, Diluent, System suitability solution, Standard solution, Sample solution, and Chromatographic system: Proceed as directed in the Assay.

Sensitivity solution: 1.5 µg/mL of USP Norelgestromin RS in Diluent from the Standard solution

System suitability

• Samples: System suitability solution, Standard solution, and Sensitivity solution
• Suitability requirements
• Resolution: NLT 1.4 between the (Z)-isomer of norelgestromin related compound A and (E)-norelgestromin, System suitability solution
• Tailing factor: 0.8–1.2 for both (E)- and (Z)-norelgestromin, Standard solution
• Relative standard deviation: NMT 0.73% for both (E)- and (Z)-norelgestromin, Standard solution
• Signal-to-noise ratio: NLT 3 for both (E)- and (Z)-norelgestromin, Sensitivity solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of each impurity in the portion of Norelgestromin taken:

Result = {r_ᵁ/[(r_ˢᴱ × F) + r_ˢᶻ]} × (C_ˢ/C_ᵁ) × 100

r_ᵁ = peak response of each impurity from the Sample solution

r_ˢᴱ = peak response of (E)-norelgestromin from the Standard solution

F = response factor for (E)-norelgestromin, 1.04

r_ˢᶻ = peak response of (Z)-norelgestromin from the Standard solution

C_ˢ = concentration of USP Norelgestromin RS in the Standard solution (mg/mL)

C_ᵁ = concentration of Norelgestromin in the Sample solution (mg/mL)

Acceptance criteria: See Table 1. Disregard peaks that are less than 0.05% of the total peak areas of (E)- and (Z)-norelgestromin.

Table 1

ᵃ (±)-13-Ethyl-17-hydroxy-18,19-dinor-17α-pregn-4-en-20-yn-3-one.

ᵇ 18,19-Dinor-17-pregn-4-en-20-yn-3-one, 17-(acetyloxy)-13-ethyl-, oxime, (17α)-(+) ; (+)-13-Ethyl-17-hydroxy-18,19-dinor-17α-pregn-4-en-20-yn-3-one oxime acetate (ester).

ᶜ (E)-Norgestimate.

ᵈ (Z)-Norgestimate.

ᵉ The combined limits for (E)- and (Z)-norgestimate are NMT 0.5%.

ᶠ 13-Ethyl-17-hydroxy-18,19-dinor-17α-pregn-5(10)-en-20-yn-3-one oxime.

ᵍ This is not a specified impurity and is included in this table for identification only. It is not to be reported or included in the total impurities.

ʰ (E)-Isomer of norelgestromin related compound A.

ᶦ (Z)-Isomer of norelgestromin related compound A.

5 SPECIFIC TESTS

5.1 Optical Rotation 〈781S〉, Procedures, Specific Rotation

Sample solution: 5 mg/mL in alcohol and water (75:25)

Acceptance criteria: +35° to +41°

5.2 Water Determination 〈921〉, Method I, Method Ic: NMT 1.0%

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in well-closed containers, and store at controlled room temperature.

USP Reference Standards 〈11〉

USP Norelgestromin RS

USP Norelgestromin Related Compound A RS

Mixture of (E)- and (Z)-isomers.

13-Ethyl-17-hydroxy-18,19-dinor-17α-pregn-5(6)-en-20-yn-3-one oxime.

C₂₁H₂₉NO₂ 327.46