Finasteride quantification in human plasma by high-performance liquid chromatography coupled to electrospray ionization tandem mass spectrometry. application to a comparative pharmacokinetics study

A specific, fast and sensitive LC-MS/MS assay was developed for the determination of finasteride in human plasma using betamethsone dipropionate as the internal standard (IS). The limit of quantification was 1.0 ng/ml and the method was linear in the range of 1.0–25.0 ng/ml. The retention times were 0.75 min for finasteride and 0.85 min for IS. Method intra-batch precision and accuracy ranged from 3.6 to 7.1%, and 96.6 to 103.9%, respectively. Inter-batch precision ranged from 2.5 to 3.4%, while Inter-batch accuracy ranged from 100.3 to 103.5%. The analytical method was applied to evaluate the pharmacokinetic and relative bioavailability of 2 different pharmaceutical formulations containing 1.0 mg of finasteride. This study evaluated 38 volunteers in a randomized, 2-period crossover study with 7 days washout period between doses. The geometric mean and respective 90% CI of finasteride test/reference percent ratios were 95.68% (91.2 – 104.6%) for Cmax, 97.5% (92.1 –103.3%) for AUC0-t and 98.1 (92.67−103.8) for AUC0-inf. Based on the 90% confidence interval of the individual ratios (test formulation/reference formulation) for Cmax and AUC0-inf, it was concluded that the test formulation is bioequivalent to the reference one with respect to the rate and extent of absorption of finasteride65944945

Avaliação de sete genótipos de sorgo (Sorghum bicolor (L.) Moench) para producao de silagem. III. Valor nutricional.

Foram estudadas a digestibilidade in vitro da matéria seca (DIVMS), a proteína bruta e os componentes da parede celular de sete genótipos de sorgo de diferentes portes e suculência do colmo para produção de silagem. A colheita do material a ser ensilado foi realizada durante o estádio de grão leitoso/pastoso, com 102 dias de idade. Na ensilagem utilizaram-se silos de laboratório, feitos de PVC. Os silos foram abertos após 7, 14,28 e 56 dias de fermentação. O teor de PB oscilou de 4,8 a 9,1 % entre os diferentes tipos de sorgo. A altura da planta não retratou a proporção de grãos e principalmente a digestibilidade do material, já que os dois sorgos de porte médio apresentaram as mais altas porcentagens de panícula e os menores valores de DIVMS. A correlação entre DIVMS e porcentagem de folhas foi positiva e entre DIVMS e componentes da parede celular foi negativa

Avaliação da silagem de sete genótipos de sorgo (Sorghum bicolor (L) Moench. III. Valor nutritivo.

Foram estudadas as silagens de quatro genótipos de sorgo de porte alto, colmo suculento e com açúcar e três de porte baixo, colmo seco e sem açúcar com o objetivo de estudar fibra em detergente neutro (FDN), fibra em detergente ácido (FDA), hemicelulose, celulose, lignina e digestibilidade in vitro da matéria seca (DIVMS). A percentagem média de FDN foi de 63,3% para os sorgos de porte alto e 65,5% para os de porte baixo. Os valores de FDA variaram de 33,1 a 35,7% no material original e de 30,1 a 34,3% aos 56 dias de ensilagem. Houve redução nos teores de hemicelulose com o avanço do processo fermentativo indicando sua utilização como fonte adicional de carboidratos. Observou-se variação nos conteúdos de celulose ao longo da fermentação em alguns dos genótipos avaliados. Os teores médios de lignina encontrados no material original e aos 56 dias de fermentação foram, respectivamente, de 5,9 e 4,6%. Em relação à DIVMS apenas o sorgo BR506 não modificou os valores com a fermentação, e o teor médio nas silagens aos 56 dias de fermentação foi de 54,8%, variação de 51,3 a 58,5%

Isolation, absolute configuration and cytotoxic activities of alkaloids from Hippeastrum goianum (Ravenna) Meerow (Amaryllidaceae)

The phytochemical study of Hippeastrum goianum led to the identification of 13 compounds by means of gas chromatography-mass spectrometry (GC-MS) and nuclear magnetic resonance (NMR). Compounds 7-demethoxy-9-O-methylhostasine (1) and 7-deoxi-trans-dihydronarciclasine (2) had their absolute configurations determined by vibrational circular dichroism (VCD). This is the first time that compound 1 is described in the Amaryllidaceae family. The cytotoxicity of all isolated compounds was tested against colorectal carcinoma (HCT 116), breast carcinoma (MCF-7), and non-tumor human retinal pigment epithelium (RPE) cell lines. The half-maximum inhibitory concentration (IC50) of compound 2 against each cell line was equivalent to the positive control (doxorubicin), indicating a considerable cytotoxic activity. Keywords: narciclasine; galasine; cytotoxic activity; absolute configuration; vibrational circular dichrois

Secretome of the preimplantation human embryo by bottom-up label-free proteomics

Abstract A bottom-up label-free mass spectrometric proteomic strategy was used to analyse the protein profiles of the human embryonic secretome. Culture media samples used for embryonic culture of patients undergoing intracytoplasmic sperm injection cycles were selected as a test case for this exploratory proof-of-principle study. The media were stored after embryo transfer and then pooled into positive (n = 8) and negative (n =8) implantation groups. The absolute quantitative bottom-up technique employed a multidimensional protein identification technology based on separation by nano-ultra-high pressure chromatography and identification via tandem nanoelectrospray ionization mass spectrometry with dataindependent scanning in a hydrid QqTOF mass spectrometer. By applying quantitative bottom-up proteomics, unique proteins were found exclusively in both the positive-and negative-implantation groups, which suggest that competent embryos express and secrete unique biomarker proteins into the surrounding culture medium. The selective monitoring of these possible secretome biomarkers could make viable procedures using singleembryo transfer

Importance of highly selective LC–MS/MS analysis for the accurate quantification of tamoxifen and its metabolites: focus on endoxifen and 4-hydroxytamoxifen

The antiestrogenic effect of tamoxifen is mainly attributable to the active metabolites endoxifen and 4-hydroxytamoxifen. This effect is assumed to be concentration-dependent and therefore quantitative analysis of tamoxifen and metabolites for clinical studies and therapeutic drug monitoring is increasing. We investigated the large discrepancies in reported mean endoxifen and 4-hydroxytamoxifen concentrations. Two published LC–MS/MS methods are used to analyse a set of 75 serum samples from patients treated with tamoxifen. The method from Teunissen et al. (J Chrom B, 879:1677–1685, 2011) separates endoxifen and 4-hydroxytamoxifen from other tamoxifen metabolites with similar masses and fragmentation patterns. The second method, published by Gjerde et al. (J Chrom A, 1082:6–14, 2005) however lacks selectivity, resulting in a factor 2–3 overestimation of the endoxifen and 4-hydroxytamoxifen levels, respectively. We emphasize the use of highly selective LC–MS/MS methods for the quantification of tamoxifen and its metabolites in biological samples

J-PAS: forecasts on interacting vacuum energy models

The next generation of galaxy surveys will allow us to test some fundamental aspects of the standard cosmological model, including the assumption of a minimal coupling between the components of the dark sector. In this paper, we present the Javalambre Physics of the Accelerated Universe Astrophysical Survey (J-PAS) forecasts on a class of unified models where cold dark matter interacts with a vacuum energy, considering future observations of baryon acoustic oscillations, redshift-space distortions, and the matter power spectrum. After providing a general framework to study the background and linear perturbations, we focus on a concrete interacting model without momentum exchange by taking into account the contribution of baryons. We compare the J-PAS results with those expected for DESI and Euclid surveys and show that J-PAS is competitive to them, especially at low redshifts. Indeed, the predicted errors for the interaction parameter, which measures the departure from a $\Lambda$CDM model, can be comparable to the actual errors derived from the current data of cosmic microwave background temperature anisotropies.Comment: 34 pages, 9 figures, 14 table