Desmetramadol

Postharvest avocado losses are mainly due to anthracnose disease caused by Colletotrichum gloeosporioides. Chemical fungicides are effective, but their negative effects on health and the environment have led to the search for sustainable alternatives such as biopolymer-based coatings and natural compounds. Therefore, chitin nanocrystals (NCChit) were extracted using a sustainable deep eutectic solvent (DES) and chemically modified into oxidized chitin nanocrystals (O-NCChit) or deacetylated chitin nanocrystals (D-NCChit) to modulate and increase the charge surface density and the dispersibility of the crystals. The modified NCChits were dispersed with silk fibroins (SF), essential oil (EO), melatonin (MT) and/or phenylalanine (Phe) to elaborate active coatings. Antioxidant and antifungal in vitro analyses showed that the O-NCChit/SF-based coating had the best performance. In addition, in vivo tests were carried out through the artificial inoculation of C. gloeosporioides on coated avocados. O-NCChit/SF/MT-based coatings reduced the severity of anthracnose by 45 %, the same effect as the chemical fungicide (Prochloraz®). Moreover, avocado quality parameters during cold storage and the shelf-life period were also evaluated, where nonsignificant differences were observed. Therefore, this study demonstrates the great potential of O-NCChit and SF in combination with active compounds for the control of anthracnose in 'Hass' avocados.

A few researches have reported the exposure-efficacy/toxicity relationships of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs). On account of the large interpatient pharmacokinetic variability, therapeutic drug monitoring (TDM) seems promising for optimizing dosage regimen and improving treatment efficacy and safety. Therefore, a rapid and convenient ultrahigh performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed and validated for the determination of icotinib, osimertinib, gefitinib and O-demesthyl gefitinib in human plasma for TDM.

Icotinib-D₄ and osimertinib-¹³CD₃ were used as the internal standards (ISs). The samples were prepared by protein precipitation using acetonitrile. Chromatographic separation was achieved on a 40 ℃ Shimadzu Shim-pack Scepter C18-120 column (2.1 ×50 mm, 3.0 µm, Japan) by a Shimadzu 30 A solvent management system. Detection was carried out using a Shimadzu LC-MS 8050CL triple quadrupole mass spectrometer coupled with an electrospray ionization source in positive mode.

This analytical method was fully validated with selectivity, carry-over, linearity, lower limit of quantification, accuracy (from 92.68% to 106.62%) and precision (intra- and inter-day coefficients of variation ranged from 0.92% to 9.85%), matrix effect, extraction recovery, stability and dilution integrity. The calibration curves were developed to be within the concentration ranges of 200-4000 ng/mL for icotinib, 50-1000 ng/mL for osimertinib, gefitinib and O-desmethyl gefitinib in human plasma which meet the needs of routine TDM.

The proposed method was used in 100 patients with non-small cell lung cancer for monitoring plasma concentration of the mentioned EGFR-TKIs. The trough concentrations of ICO were distributed between 226.42 ng/mL and 3853.36 ng/mL, peak concentrations were between 609.20 ng/mL and 2191.54 ng/mL. The trough concentrations of OSI were distributed between 110.48 ng/mL and 1183.13 ng/mL. The trough concentrations of GEF were distributed between 117.71 ng/mL and 582.74 ng/mL, while DeGEF was distributed from 76.21 ng/mL to 1939.83 ng/mL with two less than 20 ng/mL. The results of therapeutic drug monitoring aimed to investigate exposure-efficacy/toxicity relationship and improve the efficacy and safety of targeted therapies.