Naloxone and nalmefene absorption delivered by hollow microneedles compared to intramuscular injection

Naloxone and nalmefene were administered to seven research Beagle dogs, (mean weight approximately 12 kg) at a dose of 0.04 mg/kg and 0.014 mg/kg for naloxone and nalmefene, respectively. Each dose was administered intramuscularly (IM) with a standard IM injection and with a hollow microneedle device array using needles of 1 mm in length. The IM injection was delivered in the epaxial muscles, and the microneedle injection was delivered in the skin over the shoulder of each dog. Each dog received the same injections in a cross-over design. Following the injection, blood samples were collected for plasma analysis of naloxone and nalmefene by high pressure liquid chromatography with mass spectrometry detection (LCMS). The plasma sample concentrations were plotted for observed patterns of absorption and analyzed with non-compartmental pharmacokinetic methods (NCA). The results showed that the injection of naloxone from the microneedle device produced a higher peak concentration (CMAX) by 2.15x compared the IM injection of the same dose, and time to peak concentration (TMAX) was similar. For the nalmefene injection, the peak was not as high (lower CMAX) by 0.94x for the microneedle injection compared to the IM injection of the same dose. The microneedle produced an exposure, measured by area under the curve (AUC)) that was 0.85x and 0.58x as high for naloxone and nalmefene, respectively, than the injection by the IM route. We also observed that although the dose for naloxone was approximately 3x higher for naloxone compared to nalmefene, the mean peak concentration achieved from the naloxone injection was more than 12x higher than the nalmefene injection. These studies were designed to test the feasibility of using the hollow microneedle array as an effective method of naloxone and nalmefene delivery for emergency treatment of opioid-induced respiratory depression (OIRD). The results of these studies will form the basis of future studies, using the dog as a model, for development of hollow microneedle microarray devices to deliver opioid antagonists for treatment of OIRD in people.

Developments in mycotoxin analysis: an update for 2019-2020

This review summarises developments on the analysis of various matrices for mycotoxins published in the period from mid-2019 to mid-2020. Notable developments in all aspects of mycotoxin analysis, from sampling and quality assurance/quality control of analytical results, to the various detection and quantitation technologies ranging from single mycotoxin biosensors to comprehensive instrumental methods are presented and discussed. Aside from sampling and quality control, discussion of this past year’s developments is organised by detection and quantitation technology and covers chromatography with targeted or non-targeted high resolution mass spectrometry, tandem mass spectrometry, detection other than mass spectrometry, biosensors, as well as assays that use alternatives to antibodies. This critical review aims to briefly present the most important recent developments and trends in mycotoxin determination as well as to address limitations of the presented methodologies.