Norethindrone Acetate

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Cat Number

API0232105

CAS Number

51-98-9

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Product Detail Description Scientific Support Customer Q&A

CAS Number

51-98-9

EINECS

200-132-0

Storage

Store at room temperature

Synonyms

19-Norethindrone acetate; Norlutin acetate; ENTA; Norethisteron acetate; 19-Norethisterone acetate; Norethindrone 17-acetate

Molecular Formula

C22H28O3

Molecular Weight

340.5

Smiles

CC(=O)O[C@]1(CC[C@@H]2[C@@]1(CC[C@H]3[C@H]2CCC4=CC(=O)CC[C@H]34)C)C#C

Appearance

White to off-white powder

Melting Point

161-162°C

Boiling Point

454.7±45.0°C at 760 mmHg

Relative Density

1.1±0.1

General Description

Norethindrone acetate is the 17β-acetate ester of the synthetic progestin norethindrone (19-nortestosterone derivative). The acetylation enhances oral absorption and prolongs the half-life by protecting the 17β-hydroxy group from first-pass metabolism. After absorption, esterases hydrolyze the acetate group, releasing the parent progestin. The molecule retains the ethinyl group at the 17α position, conferring oral activity.

Mechanism of Action

Norethindrone acetate is a progestin that binds to progesterone receptors, inducing secretory changes in the endometrium and inhibiting gonadotropin release (LH and FSH) via negative feedback on the hypothalamic-pituitary axis. It also exhibits weak androgenic activity due to its ability to interact with androgen receptors, and minimal estrogenic or anti-estrogenic effects. The acetate prodrug form is essentially a depot of norethindrone.

Application

Norethindrone acetate is indicated for the treatment of secondary amenorrhea, abnormal uterine bleeding, and endometriosis. It is also used as a component of combination oral contraceptives (as the progestin) and as monotherapy for contraception in breastfeeding women. In hormone replacement therapy, it is combined with estrogens to prevent endometrial hyperplasia.

A population pharmacokinetic analysis of elagolix in 2168 women (healthy, with endometriosis, or with uterine fibroids) was performed using a two‑compartment model with first‑order absorption, lag time, and first‑order elimination. Only OATP1B1 genotype and body weight had statistically significant but not clinically meaningful effects on relative bioavailability and volume of distribution, respectively. No patient‑related factors or clinical parameters required dose adjustment. The approved regimen (300 mg twice daily with hormonal add‑back) is appropriate across the studied populations.

Fig. 1 Goodness-of-fit plots for the final population-pharmacokinetic model. (Beck D, et al., 2022)

References

Beck D, et al. Population Pharmacokinetics of Elagolix in Combination with Low-Dose Estradiol/Norethindrone Acetate in Women with Uterine Fibroids. Clin Pharmacokinet. 2022;61(4):577-587.

Does Norethindrone Acetate require protection from light during storage?

Yes, it is photosensitive. Light exposure can cause photodegradation and isomerization. Store in light-resistant containers, preferably amber glass.

What is the recommended storage temperature for Norethindrone Acetate?

Store at controlled room temperature (15-25°C). Avoid excessive heat above 30°C, which can accelerate hydrolysis of the acetate ester to norethindrone.

Is Norethindrone Acetate stable in tablet formulations with common excipients?

Yes, when formulated with standard excipients and protected from moisture.

How is the impurity norethindrone (free alcohol) monitored during stability?

This primary hydrolysis product is quantified using a stability-indicating HPLC method, ensuring it remains below USP/EP limits.