Quantification of estradiol cypionate in plasma by liquid chromatography coupled with tandem mass spectrometry : application in a pharmacokinetic study in healthy female volunteers

• Autor(es): Martins, Roberto Salvador, 1970- ; Antunes, Natalícia de Jesus ; Moreno, Ronilson Agnaldo ; De Nucci, Gilberto, 1958-
• Data: 2019
• Identificador Persistente: https://hdl.handle.net/20.500.12733/1643672
• Origem: Oasisbr
• Assunto(s): Acetato de medroxiprogesterona; Estradiol; Estradiol; Medroxyprogesterone acetate; LC-MS/MS; Pharmacokinetic; Monthly injectable contraceptive; Comunicação
• Tipo de Documento: Artigo científico
• Idioma: Inglês

Descrição

Agradecimentos: This study was funded by Biolab Sanus Farmacêutica Ltda., Brazil

Abstract: The combination of medroxyprogesterone acetate 25 mg + estradiol cypionate 5 mg is a highly effective, monthly injectable contraceptive. For the first time, this study presents the development and validation of a sensitive method for estradiol cypionate analysis in human plasma by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). Aliquots (500 µL) of plasma were extracted with ethyl ether (100%) and derivatized with dansyl chloride. Its separation was performed on a Jones Chromatography Genesis C8 column and the quantification was performed with a mass spectrometer equipped with an electrospray interface operating in negative ion mode. The run time was 6 min and the calibration curve was linear over the range of 0.005-0.15 ng/mL. The method was applied to evaluate the pharmacokinetics of estradiol cypionate in plasma collected up to 1008 h (42 days) after a single intramuscular administration of 25 mg/mL medroxyprogesterone acetate +5 mg/mL estradiol cypionate to healthy female volunteers (n = 12). The estradiol cypionate maximum plasma concentration (Cmax) was 0.14 ± 0.08 ng/mL reached at 16.83 ± 21.07 h and the area under the plasma concentration versus time curve (AUC0-last) was 14.07 ± 6.32 ng.h/mL. Elimination half-life (t½), apparent volume of distribution (Vd/F), apparent clearance (CL/F) and mean residence time (MRT) were 89.65 ± 76.04 h, 28038 ± 9636 L, 49.02 ± 10.62 L/h and 576.05 ± 238.32 h, respectively, showing that the estradiol cypionate release from the administration site was prolonged and there was no drug accumulation

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