Estradiol Valerate

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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1 DEFINITION

Estradiol Valerate contains NLT 98.0% and NMT 102.0% of estradiol valerate (C₂₃H₃₂O₃).

2 IDENTIFICATION

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

Change to read:

Procedure

Solution A: Water

Solution B: Acetonitrile

Mobile phase: See Table 1.

Table 1

Standard solution: 1.2 mg/mL of USP Estradiol Valerate RS in acetonitrile

Sample solution: 1.2 mg/mL of Estradiol Valerate in acetonitrile

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 220 nm

Column: 4.6-mm × 10-cm; 2.6-μm packing L87 (USP 1-Aug-2021)

Flow rate: 2.0 mL/min

Injection volume: 5 μL

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 0.73%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of estradiol valerate (C₂₃H₃₂O₃) in the portion of Estradiol Valerate taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response of estradiol valerate from the Sample solution

r_S = peak response of estradiol valerate from the Standard solution

C_S = concentration of USP Estradiol Valerate RS in the Standard solution (mg/mL)

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

Acceptance criteria: 98.0%–102.0%

4 IMPURITIES

Change to read:

Organic Impurities

Solution A, Solution B, Mobile phase, and Chromatographic system: Proceed as directed in the Assay.

System suitability solution: 1.25 mg/mL of USP Estradiol Valerate Identification Mixture RS in acetonitrile

Standard solution: 5 μg/mL of USP Estradiol Valerate RS in acetonitrile

Sample solution: 5000 μg/mL (USP 1-Aug-2021) of Estradiol Valerate in acetonitrile

System suitability

Samples: System suitability solution and Standard solution

[Note—See Table 2 for relative retention times.]

Suitability requirements

Resolution: NLT 2.5 between estradiol-9-ene valerate and estradiol valerate, System suitability solution

Relative standard deviation: NMT 10.0%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of each impurity in the portion of Estradiol Valerate taken:

Result = (r_U/r_S) × (C_S/C_U) × (1/F) × 100

r_U= peak response of each impurity from the Sample solution

r_S = peak response of estradiol valerate from the Standard solution

C_S = concentration of USP Estradiol Valerate RS in the Standard solution (μg/mL) _{(USP 1-Aug-2021)}

C_U = concentration of Estradiol Valerate in the Sample solution (μg/mL) _{(USP 1-Aug-2021)}

F = relative response factor (see Table 2)

Acceptance criteria: See Table 2. The reporting threshold is _{(USP 1-Aug-2021)} 0.05%.

Table 2

Free Acid

Diluent: Neutralize 25 mL of alcohol, in a conical flask, with 0.01 N sodium hydroxide VS to a faint blue color, using bromothymol blue TS.

Sample solution: 500 mg of Estradiol Valerate in 25 mL of Diluent

Analysis: Rapidly titrate the Sample solution with 0.01 N sodium hydroxide VS to a faint blue color. Each milliliter of 0.01 N sodium hydroxide is equivalent to 1.021 mg of valeric acid.

Acceptance criteria: NMT 0.5%, as valeric acid

5 SPECIFIC TESTS

Optical Rotation 〈781S〉, Procedures, Specific Rotation

Sample solution: 25 mg/mL, uncorrected for moisture, in methanol

Acceptance criteria: +41° to +47

Water Determination 〈921〉, Method I: NMT 0.1%

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight, light-resistant containers. Store at controlled room temperature.

USP Reference Standards 〈11〉

USP Estradiol Valerate RS

USP Estradiol Valerate Identification Mixture RS

Contains a mixture of the following 5 compounds:

Estradiol valerate.

Estradiol;

Estra-1,3,5(10)-triene-3,17β-diol.

C₁₈H₂₄O₂ 272.38

Estradiol-9-ene valerate;

3-Hydroxyestra-1,3,5(10),9(11)-tetraen-17β-yl valerate. C₂₃H₃₀O₃ 354.48

4-Methylestradiol valerate;

3-Hydroxy-4-methylestra-1,3,5(10)-trien-17β-yl valerate. C₂₄H₃₄O₃ 370.52

Estradiol divalerate;

Estra-1,3,5(10)-trien-3,17β-diyl divalerate. C₂₈H₄₀O₄ 440.61