Global treatment response analysis of velmanase alfa long term enzyme replacement therapy for alpha-mannosidosis shows treatment benefit across ages

Abstract

In the present work, the footprint of carbonyl compounds in hand scent was achieved by a miniaturized method consisting of sampling with cotton gauze, extraction and derivatization using 2,4-dinitrophenylhydrazine (DNPH) and preconcentration, separation and detection by in-tube solid-phase microextraction (IT-SPME) coupled to nano-liquid chromatography/Uv–vis diode array detection. The coupling IT-SPME-nanoLC-DAD was solved by using a two-valve system: the first valve for loading the sample and the second one to perform IT-SPME. To this aim, a nanoparticle-based capillary column was employed. Firstly, the transfer time from the load loop to the NP-based capillary column in the IT-SPME system was optimized. Additionally, the conditioning and clean-up steps were also studied. For the chromatographic separation of DNPH derivatives, gradient elution mode (acetonitrile/water) and a C18 nanocolumn were employed. The detection limits achieved were between 0.5 and 1.5 μg/L and % rsd was lower than 5% for quantification limits. The proposed methodology gave rise to different chromatographic profiles of carbonyl compounds in the hand scent of several volunteers. These profiles were obtained by estimating the relative peak area of selected carbonyls in hand scent. Nonanal, decanal and dodecanal and other low polarity carbonyl compounds (unknown hydrazones) were detected in the odor profiles.