In vivo and in vitro metabolic fate and urinary detectability of five deschloroketamine derivatives studied by means of hyphenated mass spectrometry

Ketamine derivatives such as deschloroketamine and deschloro-N-ethyl-ketamine show dissociative and psychoactive properties and their abuse as new psychoactive substances (NPSs) has been reported. Though some information is available on the biotransformation of dissociative NPSs, data on deschloro-N-cyclopropyl-ketamine deschloro-N-isopropyl-ketamine and deschloro-N-propyl-ketamine concerning their biotransformation and, thus, urinary detectability are not available. The aims of the presented work were to study the in vivo phase I and II metabolism; in vitro phase I metabolism, using pooled human liver microsomes (pHLMs); and detectability, within a standard urine screening approach (SUSA), of five deschloroketamine derivatives. Metabolism studies were conducted by collecting urine samples from male Wistar rats over a period of 24 h after their administration at 2 mg/kg body weight. The samples were analyzed using liquid chromatography high-resolution tandem mass spectrometry (LC-HRMS/MS) and gas chromatography–mass spectrometry (GC-MS). The compounds were mainly metabolized by N-dealkylation, hydroxylation, multiple oxidations, and combinations of these metabolic reactions, as well as glucuronidation and N-acetylation. In total, 29 phase I and 10 phase II metabolites were detected. For the LC-HRMS/MS SUSA, compound-specific metabolites were identified, and suitable screening targets could be recommended and confirmed in pHLMs for all derivatives except for deschloro-N-cyclopropyl-ketamine. Using the GC-MS-based SUSA approach, only non-specific acetylated N-dealkylation metabolites could be detected

Signing Information in the Quantum Era

Signatures are primarily used as a mark of authenticity, to demonstrate that the sender of a message is who they claim to be. In the current digital age, signatures underpin trust in the vast majority of information that we exchange, particularly on public networks such as the internet. However, schemes for signing digital information which are based on assumptions of computational complexity are facing challenges from advances in mathematics, the capability of computers, and the advent of the quantum era. Here we present a review of digital signature schemes, looking at their origins and where they are under threat. Next, we introduce post-quantum digital schemes, which are being developed with the specific intent of mitigating against threats from quantum algorithms whilst still relying on digital processes and infrastructure. Finally, we review schemes for signing information carried on quantum channels, which promise provable security metrics. Signatures were invented as a practical means of authenticating communications and it is important that the practicality of novel signature schemes is considered carefully, which is kept as a common theme of interest throughout this review

Pseudohyponatremia in a Patient with HIV and Hepatitis C Coinfection

Pseudohyponatremia refers to low serum sodium in the presence of normal plasma tonicity. Whereas pseudohyponatremia secondary to hyperlipidemia is a commonly recognized occurrence, falsely low sodium levels secondary to elevated protein are less frequently observed. We present in this paper the case of a man coinfected with HIV and hepatitis C who had pseudohyponatremia from hypergammaglobulinemia. As hypergammaglobulinemia is a frequent occurrence in both HIV and HCV, we suggest that pseudohyponatremia is an important and likely underdiagnosed phenomenon in this patient population. Clinicians need to be aware of the electrolyte exclusion effect and become familiar with the techniques used by their local laboratory in the measurement of serum electrolytes. Pseudohyponatremia should also be included in the differential diagnosis of an elevated osmolal gap, as the falsely lowered sodium level will lead to a falsely low calculated serum osmolality