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

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.

Intensive care medicine and the intensivist: from 1850 to 2021 / A medicina intensiva e o intensivista: de 1850 a 2021

Intensive Care Medicine gained prominence in 2020 and 2021 due to the COVID-19 pandemic. It is a recent medical specialty, which many physicians and the public know little about. This article makes a historical perspective, from the emergence of the first areas for observation of critically ill patients in the nineteenth century to the present, to the impact of the pandemic and its consequences (AU)

A Medicina Intensiva ganhou destaque no anos de 2020 e 2021 devido à pandemia por COVID-19. Trata-se de uma especialidade recente, e ainda pouco conhecida por muitos médicos e pelo público. Este artigo faz uma perspectiva histórica, desde o surgimento das primeiras áreas para observação de pacientes graves no século XIX, até o pre-sente, com o impacto da pandemia, e as perspectivas futuras (AU)