Ethanol Exposure During the Intravenous Administration of Chemotherapeutic Drugs: An Analysis of Clinical Practice and a Literature Review

PURPOSE: Injectable cytotoxics may be formulated with ethanol. This study sought to quantify the amount of ethanol exposure during chemotherapy infusions. MATERIALS AND METHODS: We first reviewed the antineoplastic drugs (Anatomical Therapeutic and Chemical code L01) and oncologic supportive care drugs (eg, antiemetics) currently available in France, to identify preparations containing ethanol. The amount of ethanol in the final chemotherapy preparation was calculated. Next, we performed a 2-year, single-center, retrospective analysis of injectable antineoplastic drug compounding in routine clinical practice in a French university medical center. Finally, we reviewed our results with regard to the literature data. RESULTS: Ten of the 60 cytotoxic products on the market contained ethanol at concentrations of up to 790 mg/mL, depending on the drug, formulation, and supplier. Several final preparations contained more than 3 g of ethanol per infusion (the maximum recommended by the European Medicines Agency); this was notably the case for gemcitabine, paclitaxel (up to 20 g ethanol per injection, for both), and etoposide (up to 50 g ethanol per infusion). The analysis of our compounding activity showed that 3,172 (4.99%) of the 63,613 chemotherapy preparations (notably paclitaxel) contained more than 3 g of ethanol. None of the oncologic supportive care drugs contained ethanol. CONCLUSION: Patients are exposed to ethanol during the infusion of antineoplastic drugs. With a view to better patient care, physicians and pharmacists should carefully evaluate the risk of ethanol exposure throughout the course of cytotoxic drug treatment.

Toilet Paper, Minced Meat and Diabetes Medicines: Australian Panic Buying Induced by COVID-19

The COVID-19 pandemic has impacted the management of non-communicable diseases in health systems around the world. This study aimed to understand the impact of COVID-19 on diabetes medicines dispensed in Australia. Publicly available data from Australia’s government subsidised medicines program (Pharmaceutical Benefits Scheme), detailing prescriptions by month dispensed to patients, drug item code and patient category, was obtained from January 2016 to November 2020. This study focused on medicines used in diabetes care (Anatomical Therapeutical Chemical code level 2 = A10). Number of prescriptions dispensed were plotted by month at a total level, by insulins and non-insulins, and by patient category (general, concessional). Total number of prescriptions dispensed between January and November of each year were compared. A peak in prescriptions dispensed in March 2020 was identified, an increase of 35% on March 2019, compared to average growth of 7.2% in previous years. Prescriptions dispensed subsequently fell in April and May 2020 to levels below the corresponding months in 2019. These trends were observed across insulins, non-insulins, general and concessional patient categories. The peak and subsequent dip in demand have resulted in a small unexpected overall increase for the period January to November 2020, compared to declining growth for the same months in prior years. The observed change in consumer behaviour prompted by COVID-19 and the resulting public health measures is important to understand in order to improve management of medicines supply during potential future waves of COVID-19 and other pandemics.

Proposal of the Annotation of Phosphorylated Amino Acids and Peptides Using Biological and Chemical Codes

Phosphorylation represents one of the most important modifications of amino acids, peptides, and proteins. By modifying the latter, it is useful in improving the functional properties of foods. Although all these substances are broadly annotated in internet databases, there is no unified code for their annotation. The present publication aims to describe a simple code for the annotation of phosphopeptide sequences. The proposed code describes the location of phosphate residues in amino acid side chains (including new rules of atom numbering in amino acids) and the diversity of phosphate residues (e.g., di- and triphosphate residues and phosphate amidation). This article also includes translating the proposed biological code into SMILES, being the most commonly used chemical code. Finally, it discusses possible errors associated with applying the proposed code and in the resulting SMILES representations of phosphopeptides. The proposed code can be extended to describe other modifications in the future.

Mass spectrometric sample identification with indicator compounds introduced via labeled sample tubes

ObjectivesThe risk of sample confusion continues to be a challenge for the pre-analytical part of the overall testing process. We here describe a novel system to track samples based on a chemical code labeling of test tubes with unique combinations of indicator compounds, which are naturally not present in specimens of human origin. As part of the sample vessel filling, the liquid specimens are permanently labeled with the compound code that can be tracked back to the primary tube.MethodsAs a proof of concept we used 10 stable-isotope-labeled derivates of medical drugs as indicator substances to create a combinatory 10-digit binary number ID for individual test tubes, i.e. presence/absence of the respective compound. For this purpose, combinations of indicator compounds were provided in evaporated form in polypropylene tubes prior to filling with anonymized patient whole blood and corresponding plasmas subjected to liquid chromatography tandem-mass spectrometry designed to detect the 10 indicator compounds.ResultsIn the blind analysis, we correctly identified 307 different whole blood samples by readout of a 10-digit binary number ID based on the detection of indicator compounds with respect to their presence and number.ConclusionsWe have demonstrated the feasibility of an internal labeling procedure for diagnostic samples with mass spectrometry-based readout of dissolved indicator compound combinations as a binary number ID. With an increasing number of coding compounds (≫10) a vast number of combinations for sample labeling can be realized beyond the proof of concept setting studied herein.

Using weapons instead of perfume – chemical association strategies of the myrmecophilous bug Scolopostethus pacificus (Rhyparochromidae)

A vast diversity of parasites associate with ants. Living in and around ant nests these organisms must overcome ant colony defenses. As ant defensive behavior is mainly mediated by species-specific cuticular hydrocarbons (CHCs) or alarm pheromones, ant-associated parasites can either crack their hosts chemical communication code by modifying their own CHC-profiles or use pro-active strategies like chemical weaponry for distraction and repellency. While the chemical nature of ant-parasite interactions has been intensively studied for highly host specific parasites, the chemical-deceptive strategies of the rather rare ant-resembling Heteropterans are unknown. To gain insight into this system, I studied the bug Scolopostethus pacificus (Barber 1918) which can be found near the nests of the ecologically dominant and aggressive velvety tree ant (Liometopum occidentale, Emery 1895). Using behavioral, chemical and molecular approaches I disentangled the relationship of S. pasificus and its host ant. Chemical profiling of the bug and the ant revealed that the bug does not make use of CHC insignificance or mimicry, but instead uses a cocktail of volatile compounds released from its metathoracic glands that likely moderates encounters with its aggressive host. Feeding trials with armed and artificially disarmed bugs revealed a defensive function of the gland exudates. Targeted molecular gut barcoding showed that S. pasificus does not feed on L. occidentale. These results suggest that chemical weaponry, rather than a chemical code-cracking CHC matching or chemical insignificance, enables S. pasificus to get along with and live in close proximity to its host ant.

Species cycling and the enhancement of ammonia in pre-stellar cores

ABSTRACT The quantity of NH3 produced on grain surfaces in the pre-stellar core is thought to be one of the determining factors regarding the chemical complexity achievable at later stages of stellar birth. In order to investigate how this quantity might be influenced by the gas–grain cycling of molecular material within the cloud, we employ a modified rates gas–grain chemical code and follow the time-dependent chemistry of NH3 as the system evolves. Our models incorporate an updated version of the most recent UDfA network of reaction rate coefficients, desorption from the grains through standard thermal and non-thermal processes, and physisorbed and chemisorbed binding of atomic and molecular hydrogen to a population of carbonaceous and siliceous grains. We find that (1) observable abundances of NH3 can exist in the gas phase of our models at early times when the N atom is derived from CN via an efficient early-time hydrocarbon chemistry, (2) a time-dependent gradient exists in the observational agreement between different species classes in our models, consistent with possible physical substructures within the TMC-1 Cyanopolyyne Peak, and (3) the gaseous and solid-state abundances of NH3 are sensitive to the presence of gas–grain cycling within the system. Our results suggest that the degree of chemical complexity achievable at later stages of the cloud’s chemical evolution is indeed influenced by the manner in which the gas–grain cycling occurs.

A universal system for digitization and automatic execution of the chemical synthesis literature

Robotic systems for chemical synthesis are growing in popularity but can be difficult to run and maintain because of the lack of a standard operating system or capacity for direct access to the literature through natural language processing. Here we show an extendable chemical execution architecture that can be populated by automatically reading the literature, leading to a universal autonomous workflow. The robotic synthesis code can be corrected in natural language without any programming knowledge and, because of the standard, is hardware independent. This chemical code can then be combined with a graph describing the hardware modules and compiled into platform-specific, low-level robotic instructions for execution. We showcase automated syntheses of 12 compounds from the literature, including the analgesic lidocaine, the Dess-Martin periodinane oxidation reagent, and the fluorinating agent AlkylFluor.