High-fidelity teleportation of a logical qubit using transversal gates and lattice surgery.

Quantum state teleportation is commonly used in designs for large-scale quantum computers. Using Quantinuum's H2 trapped-ion quantum processor, we demonstrate fault-tolerant state teleportation circuits for a quantum error correction code-specifically the Steane code. The circuits use up to 30 qubits at the physical level and employ real-time quantum error correction.

Development of a sensitive LC-MS/MS assay to support human microdose study for an oral agonist of the GLP-1 receptor.

The purpose of this work was to determine the feasibility of supporting a clinical microdose study for PF-06882961 (danuglipron), an oral small molecule agonist of the GLP-1 receptor, by LC-MS/MS. Statistical instrument parameter optimization using response surface methodology was employed to develop a LC-MS/MS method for the analyte, PF-06882961. An LC-MS/MS method was developed and validated to support a proof of concept microdose pharmacokinetics preclinical study in monkeys, administered PF-06882961 (0.

Inception and development of a LC-MS/MS assay for the multiplexed quantitation of nine human drug transporter biomarkers.

It has become common practice to assess solute carrier transporter (SLC)-mediated drug-drug interactions (DDIs) by quantitating various individual endogenous compounds as biomarkers in human plasma and urine. The goal of this work was to develop biomarker multiplex assays that could be utilized during first in human studies to support the simultaneous assessment of clinical DDI risk across various SLCs. Hydrophilic interaction chromatography-MS/MS methods were developed, and validations were performed.

LC-MS/MS method for the quantitation of OCT1 biomarker isobutyrylcarnitine in human plasma with clinical sample analysis.

Isobutyrylcarnitine (IBC) is a possible biomarker for hepatic OCT1, as IBC plasma concentrations are reduced when OCT1 is inhibited. An accessible, characterized assay is needed to quantitate IBC in human plasma. A triple quadrupole MS surrogate matrix assay for the quantitation of IBC was characterized to support a first-in-human study.

Development and implementation of urinary transporter biomarkers to facilitate assessment of drug-drug interaction.

Novel urinary biomarker evaluation approaches to support inhibition assessment for renal transporters (e.g., OCT2, multidrug and toxin extrusion proteins [MATEs]).

Radium Ion Optical Clock.

We report the first operation of a Ra^{+} optical clock, a promising high-performance clock candidate. The clock uses a single trapped ^{226}Ra^{+} ion and operates on the 7s ^{2}S_{1/2}→6d ^{2}D_{5/2} electric quadrupole transition. By self-referencing three pairs of symmetric Zeeman transitions, we demonstrate a frequency instability of 1.

A novel hydrophilic interaction chromatography assay characterization of 4-pyridoxic acid, an emergent renal organic anion transporter 1/3 transporter biomarker.

4-pyridoxic acid (PDA) has been proposed as an endogenous biomarker for renal organic anion transporter 1/3 (OAT1/3) inhibition. Clinical data are needed to support the proposal. A hydrophilic interaction chromatography (HILIC)-LC/MS/MS assay was developed and characterized to support clinical drug-drug interaction (DDI) studies.

Optical Mass Spectrometry of Cold RaOH^{+} and RaOCH_{3}^{+}.

We present an all-optical mass spectrometry technique to identify trapped ions. The new method uses laser-cooled ions to determine the mass of a cotrapped dark ion with a sub-dalton resolution within a few seconds. We apply the method to identify the first controlled synthesis of cold, trapped RaOH^{+} and RaOCH_{3}^{+}.

A Multiplexed HILIC-MS/HRMS Assay for the Assessment of Transporter Inhibition Biomarkers in Phase I Clinical Trials: Isobutyryl-Carnitine as an Organic Cation Transporter (OCT1) Biomarker.

There is a growing interest in using endogenous compounds as drug transporter biomarkers to facilitate drug-drug interaction (DDI) risk assessment in early phase I clinical trials. Compared to other drug transporters, however, no valid biomarker for hepatic organic cation transporter (OCT) 1 has been described to date. The present work represents the first report of an endogenous compound, isobutyryl-l-carnitine (IBC), as a potential clinical OCT1 biomarker for DDI assessment.

Evaluation of OptiFlow™-MS/MS for bioanalysis of pharmaceutical drugs and metabolites.

Microflow tandem mass spectrometry-based methods have been proposed as options to improve sensitivity and selectivity while improving sample utility and solvent consumption. Here, we evaluate a newly introduced microflow source, OptiFlow™, for quantitative performance. We performed a comparison of the OptiFlow and IonDrive™ sources, respectively, on the same triple quadrupole mass spectrometer.

2019 White Paper on Recent Issues in Bioanalysis: Chromatographic Assays (Part 1 - Innovation in Small Molecules and Oligonucleotides & Mass Spectrometric Method Development Strategies for Large Molecule Bioanalysis).

The 2019 13 Workshop on Recent Issues in Bioanalysis (WRIB) took place in New Orleans, LA, USA on April 1-5, 2019 with an attendance of over 1000 representatives from pharmaceutical/biopharmaceutical companies, biotechnology companies, contract research organizations and regulatory agencies worldwide. WRIB was once again a 5-day, week-long event - a full immersion week of bioanalysis, biomarkers, immunogenicity and gene therapy. As usual, it was specifically designed to facilitate sharing, reviewing, discussing and agreeing on approaches to address the most current issues of interest including both small- and large-molecule bioanalysis involving LCMS, hybrid LBA/LCMS, LBA cell-based/flow cytometry assays and qPCR approaches.

Bioanalysis of Targeted Nanoparticles in Monkey Plasma via LC-MS/MS.

This work represents the first reporting of a comprehensive bioanalytical GLP methodology detailing the mass spectrometric quantitation of PF-05212384 dosed as a targeted polymeric encapsulated nanoparticle (PF-07034663) to monkeys. Polymeric nanoparticles are a type of drug formulation that enables the sustained release of an active therapeutic agent (payload) for targeted delivery to specific sites of action such as cancer cells. Through the careful design and engineering of the nanoparticle formulation, it is possible to improve the biodistribution and safety of a given therapeutic payload in circulation.

Laser Cooling of Radium Ions.

The unstable radium nucleus is appealing for probing new physics due to its high mass, octupole deformation, and energy level structure. Ion traps, with long hold times and low particle numbers, are excellent for work with radioactive species, such as radium and radium-based molecular ions, where low activity, and hence low total numbers, is desirable. We address the challenges associated with the lack of stable isotopes in a tabletop experiment with a low-activity (∼10  μCi) source where we laser-cool trapped radium ions.

LC-MS/MS assay for N-methylnicotinamide in humans, an endogenous probe for renal transporters.

Background: N-methylnicotinamide (1-NMN) has been proposed as a potential clinical biomarker to assess drug-drug interactions involving organic cation transporters (OCT2) and multidrug and toxin extrusion protein transporters.

Results: A hydrophilic interaction liquid chromatography-MS/MS assay, to quantify 1-NMN, in human plasma and urine is reported.

Materials & Methods: A hydrophilic interaction chromatography (HILIC)-tandem mass spectrometry (MS/MS) assay to quantify 1-NMN in human plasma and urine is reported.

A fully automated and validated human plasma LC-MS/MS assay for endogenous OATP biomarkers coproporphyrin-I and coproporphyrin-III.

Aim: A validated LC-MS/MS assay for the quantitation of coproporphyrin-I and -III (CP-I, CP-III) in human plasma has been developed to understand the utility of both as possible endogenous biomarkers for organic anion-transporting polypeptides (OATP)-mediated drug-drug interactions (DDIs).

Materials And Methods:  Human plasma extracts were analyzed for CP-I and CP-III using a Sciex API 6500+ mass spectrometer. Results: The assay was utilized for plasma samples from a clinical DDI study involving a new chemical entity that presented as an OATP inhibitor in vitro.

A sensitive method for the quantitation of the peptide-based glucagon-like peptide-1 receptor agonist liraglutide in plasma using microfluidics chromatography tandem MS.

Aim: An LC-MS/MS assay for the quantitation of liraglutide, a peptide-based injectable glucagon-like peptide-1 receptor agonist, has been developed as a convenient alternative to the enzyme-linked immunosorbent assay, and used to characterize liraglutide pharmacokinetics in cynomolgus monkeys.

Results: Assay calibration curves exhibited a linear dynamic range of 10-5000 ng/ml and correlation coefficient ≥0.98.

A highly selective and sensitive LC-MS/HRMS assay for quantifying coproporphyrins as organic anion-transporting peptide biomarkers.

Aim: Coproporphyrin-I (CP-I) and coproporphyrin-III (CP-III) in plasma and urine have been proposed as biomarkers for assessing drug-drug interactions involving hepatic drug transporters such as organic anion-transporting peptides (OATP), 1B1 and 1B3. Materials & methods: Plasma and urine extracts were analyzed for CP-I/CP-III using a TripleTOF API6600 mass spectrometer. Results: Previously unreported, CP-I/CP-III doubly charged ions (m/z 328.

Small molecule specific run acceptance, specific assay operation, and chromatographic run quality assessment: recommendation for best practices and harmonization from the global bioanalysis consortium harmonization teams.

Consensus practices and regulatory guidance for liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) assays of small molecules are more aligned globally than for any of the other bioanalytical techniques addressed by the Global Bioanalysis Consortium. The three Global Bioanalysis Consortium Harmonization Teams provide recommendations and best practices for areas not yet addressed fully by guidances and consensus for small molecule bioanalysis. Recommendations from all three teams are combined in this report for chromatographic run quality, validation, and sample analysis run acceptance.

Bioanalysis zone: DBS survey results.

Bioanalysis Zone carried out a survey to evaluate the use of and attitudes to DBS analysis among our readership in the bioanalytical community. DBS analysis has generated a huge amount of interest in recent years. We wanted to take a snapshot of the field and determine whether a consensus is emerging on the future of DBS.

Utilization of hydrophilic-interaction LC to minimize matrix effects caused by phospholipids.

Background: In bioanalysis, phospholipids may affect the precision and accuracy of LC-MS/MS methods and compromise the quality of the results, especially when samples in complex biomatrices are extracted by protein precipitation techniques.

Results: It was found that the retentive behavior of both common pharmaceuticals and physiologically relevant phospholipids under bare silica hydrophilic-interaction LC (HILIC) is more predictable than under reversed-phase conditions. In particular, the retention time of phospholipids was not significantly affected by varying the salt and acid modifiers in the mobile phases, but common pharmaceuticals can be shifted away from these phospholipid interferences through mobile phase modifiers.

International Federation for Emergency Medicine Model Curriculum for Emergency Medicine Specialists.

To meet a critical and growing need for emergency physicians and emergency medicine resources worldwide, physicians must be trained to deliver time-sensitive interventions and lifesaving emergency care. Currently, there is no globally recognized, standard curriculum that defines the basic minimum standards for specialist trainees in emergency medicine. To address this deficit, the International Federation for Emergency Medicine convened a committee of international physicians, health professionals and other experts in emergency medicine and international emergency medicine development to outline a curriculum for training of specialists in emergency medicine.

The efficacy and value of emergency medicine: a supportive literature review.

Study Objectives: The goal of this study was to identify publications in the medical literature that support the efficacy or value of Emergency Medicine (EM) as a medical specialty and of clinical care delivered by trained emergency physicians. In this study we use the term "value" to refer both to the "efficacy of clinical care" in terms of achieving desired patient outcomes, as well as "efficiency" in terms of effective and/or cost-effective utilization of healthcare resources in delivering emergency care. A comprehensive listing of publications describing the efficacy or value of EM has not been previously published.

Application of the dried spot sampling technique for rat cerebrospinal fluid sample collection and analysis.

Dried blood spotting (DBS) sample collection is gaining favor in the pharmaceutical industry due to benefits that include reduced animal usage and easier sample shipment and storage when compared to traditional plasma collection/analysis. The applicability of the DBS card to alternate, limited-volume, matrices has not been as fully characterized as their use with whole blood. In this paper we explored the application of the DBS sample collection technique to rat cerebrospinal fluid (CSF).

International Federation for Emergency Medicine model curriculum for medical student education in emergency medicine.

There is a critical and growing need for emergency physicians and emergency medicine resources worldwide. To meet this need, physicians must be trained to deliver time-sensitive interventions and life-saving emergency care. Currently, there is no internationally recognized, standard curriculum that defines the basic minimum standards for emergency medicine education.

Comparison of trauma mortality between two hospitals in Turkey to one trauma center in the US.

Objectives: The development of comprehensive international trauma case registries could be used to perform outcomes analysis and comparisons between countries with the goal of improving trauma care worldwide.

Methods: A retrospective study (April 2004 to April 2005) of injured patients from a Pennsylvania state trauma center (PSTC) were case matched according to age, sex, and injury severity score with two Turkish hospitals. Patients' demographics (age, sex), prehospital information (mechanism of injury, mode of transportation), injury severity (injury severity score and Glasgow coma score), and outcomes (intensive care unit length of stay, hospital length of stay, mortality) were collected.