High Resolution Ion Mobility Enables the Structural Characterization of Atropisomers of GDC-6036, a KRAS G12C Covalent Inhibitor.

GDC-6036 is a covalent KRAS G12C inhibitor that demonstrates high potency and selectivity. Structurally, GDC-6036 consists of several motifs that make the analytical characterization of this molecule challenging, including a highly basic pyrrolidine motif bonded to a quinazoline ring via an ether bond and an atropisomeric carbon-carbon bond between functionalized pyridine and quinazoline groups. Structurally, the desired atropisomer was synthesized via an atroposelective Negishi coupling with very high yield.

Automated online deconjugation of antibody-drug conjugate for small molecule drug profiling.

Antibody-drug conjugates (ADCs) are designed by chemically linking highly potent cytotoxic small molecule drugs to monoclonal antibodies of unique specificity for targeted destruction of cancer cells. This innovative class of molecules incurs unique developmental challenges due to its structural complexity of having both small molecule and protein components. The stability of the small molecule payload on the ADC is a critical attribute as it directly relates to product efficacy and patient safety.

Development of a Near-Infrared Spectroscopy (NIRS)-Based Characterization Approach for Inherent Powder Blend Heterogeneity in Direct Compression Formulations.

With the advent of continuous direct compression (CDC) process, it becomes increasingly desirable to characterize inherent powder blend heterogeneity at a small batch scale for a robust and CDC-amenable formulation. To accomplish this goal, a near infrared spectroscopy (NIRS)-based characterization approach was developed and implemented on multiple direct compression (DC) blends in this study, with the intended purpose of complementing existing formulation development tools and enabling to build an early CMC data package for late-phased process analytical technology (PAT) method development. Three fumaric acid DC blends, designed to harbor varied degrees of inherent blend heterogeneity, were employed.

Corrigendum to "Mixed methods feasibility study for the surviving opioid overdose with naloxone education and resuscitation (SOONER) trial" [Resuscitation Plus 6 (2021) 100131].

[This corrects the article DOI: 10.1016/j.resplu.

Mixed methods feasibility study for the surviving opioid overdose with naloxone education and resuscitation (SOONER) trial.

Aim: We plan to conduct a randomised clinical trial among people likely to witness opioid overdose to compare the educational effectiveness of point-of-care naloxone distribution with best-available care, by observing participants' resuscitation skills in a simulated overdose. This mixed methods feasibility study aims to assess the effectiveness of recruitment and retention strategies and acceptability of study procedures.

Methods: We implemented candidate-driven recruitment strategies with verbal consent and destigmatizing study materials in a family practice, emergency department, and addictions service.

Clinical Characteristics and Remedy Profiles of Patients with COVID-19: A Retrospective Cohort Study.

Objective: The aim of the study was to identify indicated homeopathic remedies based on the clinical characteristics of coronavirus disease 2019 (COVID-19) patients in India.

Methods: In this retrospective, cohort study, confirmed COVID-19 patients admitted at a COVID Health Centre in New Delhi between April 29 and June 17, 2020 were given conventional and homeopathic treatment. Patients were grouped into mild, moderate or severe categories of disease.

Simultaneous quantitation of water and residual solvents in pharmaceuticals by rapid headspace gas chromatography with thermal conductivity detection (GC-TCD).

In the pharmaceutical industry, an array of analytical testing is performed to demonstrate the safety and efficacy of drug substance and drug products. Among the most critical attributes of release testing are quantitation of residual solvents from the manufacturing process, which pose toxicity concerns, and determination of water content, which can impact potency and shelf life. Residual solvent determination in pharmaceuticals is most commonly performed using headspace capillary gas chromatography (GC) with flame ionization detection (FID), a robust technique that incorporates a mode of detection noteworthy for its sensitivity and wide dynamic range.

Ideals of the Multiview Variety.

The multiview variety of an arrangement of cameras is the Zariski closure of the images of world points in the cameras. The prime vanishing ideal of this complex projective variety is called the multiview ideal. We show that the bifocal and trifocal polynomials from the cameras generate the multiview ideal when the foci are distinct.