BIOEQUIVALENCE STUDY OF A 400 MG INTRAVAGINAL PROGESTERONE PESSARY USING TANDEM MASS SPECTROMETRY IN FEMALE SUBJECTS

AHMAD ABU-AWWAD; BASIL ARAFAT; TAWFIQ ARAFATE

doi:10.22159/ijap.2025v17i4.53648

Authors

AHMAD ABU-AWWAD Faculty of Pharmacy, Jerash University, P. O. Box 311, Jerash-26150, Jordan
BASIL ARAFAT Jordan Center for Pharmaceutical Research, P. O. Box 950435, Amman-11105, Jordan. Faculty of Health, Education, Medicine and Social Care, Anglia Ruskin University, Chelmsford Campus, UK
TAWFIQ ARAFATE Jordan Center for Pharmaceutical Research, P. O. Box 950435, Amman-11105, Jordan

DOI:

https://doi.org/10.22159/ijap.2025v17i4.53648

Keywords:

Progesterone, Bioequivalence, LC-MS/MS, Method validation, Pilot study

Abstract

Objective: This study aimed to evaluate the bioequivalence of 400 mg single pessary dose for intravaginal progesterone test product in pilot study followed by a full study compared to the reference product, Cyclogest^®. The test product represents a newly developed intravaginal progesterone formulation designed to achieve bioequivalent Pharmacokinetic (PK) parameters to Cyclogest^®.

Methods: The test product was initially studied in six healthy adult females following a randomized, two-way crossover design under fasted state. The results from the pilot study were further confirmed in full study of 38 subjects. Progesterone with progesterone-D9 as the internal standard, was extracted and quantified from human plasma samples using LC-MS/MS after a direct precipitation extraction procedure. The developed method was validated over a dynamic range of 0.3–25 ng/ml in accordance with US-FDA, EMEA, and ICH guidelines.

Results: All validation results were within the acceptance criteria. The geometric mean values for the main PK parameters from the pilot bioequivalence study for the test product were C_max= 13.094 ng/ml and AUC_0-t= 168.786 h. ng/ml, compared to the results of reference product (C_max=11.920 ng/ml and AUC_0-t = 154.339 h. ng/ml), which were in agreement with the corresponding results obtained from the full study for test product (C_max= 15.175 ng/ml and AUC_0-t = 202.669 h. ng/ml) compared to the results of reference product (C_max= 13.359 ng/ml and AUC_0-t = 206.423 h. ng/ml).

Conclusion: The investigated test progesterone product was bioequivalent to the reference product.

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