Determination of docetaxel in dried blood spots by LC-MS/MS: Method development, validation and clinical application.

In this study, a LC-MS/MS method for the measurement of docetaxel in Dried Blood Spots (DBS) samples was developed and validated. Docetaxel was extracted from 8 mm DBS punch with a mixture of methanol and acetonitrile (9:1, v/v). The chromatographic separation occurred in an Acquity® C18 column (150 × 2.1 mm, 1.7 µm) eluted with a mixture of water and acetonitrile plus 0.1% formic acid (45:55, v/v). Total analytical run time was 7 min. The method was linear from 50 to 3000 ng ml-1. Precision assays showed CV% < 9.8% and accuracy between 99 and 103%, mean recovery was 81%. The method was applied in the determination of the docetaxel in 31 patients, after collection of two paired venous blood and DBS samples, following a limited sampling strategy protocol. The analyte was stable in DBS for 18 days at 25 °C and 9 days at 45 °C. The interval of docetaxel concentrations measured in DBS collected before the end of the infusion was 756-3047 ng ml-1 and 60 ±â€¯10 min after the end of the infusion was 57-331 ng ml-1. AUC values calculated from DBS-derived estimated plasma concentrations (EPC) represented on average 100% of those obtained in plasma samples of 3.1 mgh/l (2.4-4.9 mg h/l). There was a 93% agreement between the classification of patients as within or without the therapeutic range by plasma and EPC AUC. These findings support the clinical use of DBS sampling for routine therapeutic drug monitoring of docetaxel.

Estudio de Fiebre Amarilla en primates en áreas de brote de los departamentos de San Pedro y Central del Paraguay / Study of Yellow Fever in primates in outbreaks areas of the departments of San Pedro and Central in Paraguay

La Fiebre Amarilla (FA) es una de las más importantes zoonosis que afecta a poblaciones humanas. La FA silvestre es imposible de ser erradicada, manteniéndose activa en zonas tropicales en África y Sudamérica. Todas las especies de primates son susceptibles y se consideran reservorios en el medio silvestre. La mortalidad es baja, se desconoce su valor con precisión, sin embargo existen epizootias con alta mortalidad, en humanos varía entre 20-50%. El objetivo de este trabajo fue buscar evidencias de FA en primates capturados en áreas de brote de FA de los departamentos de San Pedro y Central del Paraguay mediante la técnica de Neutralización por reducción de placas para FA cepa vacunal 17 D. Los resultados en los 35 primates estudiados fueron negativos, quizás por lo tardío del momento en la toma de muestras y bajo número de primates capturados.

Yellow Fever (YF) is one of the most important zoonotic diseases affecting human population. It is impossible to eradicate wild YF remaining active in tropical zones of Africa and South America. All species of primates are susceptible and are considered reservoirs in wild regions. Mortality is low and its precise value is unknown though there are epizootics with high mortality rates and in humans varies between 20-50%. The objective of this study was to search for evidence of YF in primates caught in YF outbreaks areas of the departments of San Pedro and Central in Paraguay through the neutralization technique by plates reduction for YF vaccine strain 17 D. The results in the 35 primates studied were negative, perhaps because of the lateness of the time sampling and the low number of captured primates.