BACKGROUND: Cloxacillin and flucloxacillin are prone to degradation and polymerization in humid and hot environments, and their polymers have long been recognized to trigger allergic manifestations. A series of the degradation and polymerized impurities in cloxacillin and flucloxacillin were separated and characterized to ensure safe use of these drugs by the public.
METHODS: By studying the chromatographic behavior of the degradation impurities and polymerized impurities in reversed-phase high-performance liquid chromatography (RP-HPLC) gradient elution, the impurities in cloxacillin and flucloxacillin were effectively separated and eluted. RP-HPLC tandem ion trap/time-of-flight mass spectrometry (MS) was applied to characterize the structures of unknown impurities eluted from the RP-HPLC methods for cloxacillin and flucloxacillin. The mechanisms of formation of the impurities in cloxacillin and flucloxacillin were also investigated.
RESULTS: The structures of 10 unknown impurities in cloxacillin and 8 unknown impurities in flucloxacillin were elucidated based on the high-resolution MSn data at positive and negative modes, respectively. Six polymerized impurities were found and characterized, of which three were from the polymerization of cloxacillin and three were from the polymerization of flucloxacillin.
CONCLUSIONS: The study on the impurity profiles of cloxacillin and flucloxacillin provided a scientific basis for improving their production processes and quality control.

The illegal drug market is constantly evolving, with new drugs being created and existing ones being modified. Adulterants are often added to the mix, and the primary substance may be secretly replaced by a new one. Once-known tablets can now be vastly different from what they are sold as, all due to the pursuit of profit and evasion of current drug regulations. These alterations in drug composition pose a threat to society, as their effects are still not well understood. Therefore, it is crucial for police intelligence and public health development to obtain the chemical profiles of illicit drugs. This study presents the chemical fingerprinting of ecstasy tablets seized in the state of Rio de Janeiro (Brazil) between 2012 and 2021. The tablet samples were weighed, extracted, diluted with methanol, and acidified before analysis using gas chromatography high-resolution mass spectrometry and attenuated total reflection Fourier transform infrared spectroscopy. The major constituents found were MDMA and clobenzorex, with fewer occurrences of MDA, MDEA, and 2C-B. The results also indicate that the occurrence of mega-events in the study location impacted the chemical fingerprints of ecstasy. A total of 27 combinations of cutting agents, including caffeine, ephedrine, and anesthetics, were identified. Samples composed of clobenzorex were observed throughout the evaluated period in areas near highways, suggesting that this product is mainly used by truck drivers. These findings can help police intelligence units anticipate the behavior of the illicit market during major events, identify traffic routes, and support public health initiatives.

BACKGROUND: Lomefloxacin hydrochloride ear drops are highly unstable to light and prone to produce photodegradation impurities. These impurities might be related to the phototoxicity of lomefloxacin, which could seriously threaten the health of patients. In this article, the photodegradation impurity profile in lomefloxacin hydrochloride ear drops was studied for further improvement of quality control of the drug.
METHODS: By studying the chromatographic behavior of photodegradation impurities, the photodegradation impurities in lomefloxacin hydrochloride ear drops were separated and detected effectively. Liquid chromatography combined with ion trap/time-of-flight mass spectrometry was applied to characterize the structures of the photodegradation impurities in lomefloxacin hydrochloride ear drops.
RESULTS: The structures of 17 impurities in lomefloxacin hydrochloride ear drops were elucidated based on high-resolution MSn data in positive ion mode, 12 of them being unknown impurities.
CONCLUSIONS: The structural characteristics and fragmentation patterns of the photodegradation impurities were also studied. The study of the photodegradation impurity profile in lomefloxacin hydrochloride ear drops provides a scientific basis for quality control of these ear drops and ensures the safety of drug use by the public.

External contamination of hair by cannabis smoking requires a careful evaluation in forensic toxicology. Medical and recreational cannabis are increasingly consumed by e-cigarettes, which give rise to side-stream vapor. Moreover, products containing low Δ9-tetrahydrocannabinol (Δ9-THC) and rich in cannabidiol (CBD) started spreading legally. The goal of the present study was to assess whether hair analysis could allow to distinguish the type of delivered product, with low or high Δ9-THC, and the delivering mode, by smoking or vaping. Contamination of blank hair was mimicked by in vitro exposure to low- (0.4%) and high-Δ9-THC (9.7%) products delivered by smoking and vaping within a small confined system. Cannabis vaping extracts were prepared to deliver identical target Δ9-THC doses. Eighty samples were analyzed by ultrahigh-performance liquid chromatography mass spectrometry and quantified for Δ9-THC and CBD. After contamination by cannabis smoking, THC levels were in line with past in vitro and in vivo studies. Samples exposed to cannabis (169.30 ng/mg) showed significantly higher Δ9-THC than hair exposed to \"light cannabis\" (35.54 ng/mg), and the opposite was seen for the CBD/Δ9-THC ratio. Hair contaminated by vaping or smoking did not show a statistically different Δ9-THC content. Under our in vitro conditions, hair analysis might allow to discriminate whether external contamination is determined by products containing low or high Δ9-THC, but not the delivering mode. More research is needed in real-life conditions, to see whether the same also applies to the interpretation of forensic casework.

Environmental testing of high-touch objects is a potential noninvasive approach for monitoring population-level trends of SARS-CoV-2 and other respiratory viruses within a defined setting. We aimed to determine the association between SARS-CoV-2 contamination on high-touch environmental surfaces, community level case incidence, and university student health data. Environmental swabs were collected from January 2022 to November 2022 from high-touch objects and surfaces from five locations on a large university campus in Florida, USA. RT-qPCR was used to detect and quantify viral RNA, and a subset of positive samples was analyzed by viral genome sequencing to identify circulating lineages. During the study period, we detected SARS-CoV-2 viral RNA on 90.7 % of 162 tested samples. Levels of environmental viral RNA correlated with trends in community-level activity and case reports from the student health center. A significant positive correlation was observed between the estimated viral gene copy number in environmental samples and the weekly confirmed cases at the university. Viral sequencing data from environmental samples identified lineages concurrently circulating in the local community and state based on genomic surveillance data. Further, we detected emerging variants in environmental samples prior to their identification by clinical genomic surveillance. Our results demonstrate the utility of viral monitoring on high-touch environmental surfaces for SARS-CoV-2 surveillance at a community level. In communities with delayed or limited testing facilities, immediate environmental surface testing may considerably inform epidemic dynamics.

Mass balance in drug substances release testing is a critical quality attribute in pharmaceutical manufacturing that continues to challenge modern analytical characterization. This specific perspective of mass balance is lacking in literature, and the following work addresses the knowledge gap related to this topic by examining an in-depth case study and detailing the systematic investigation into mass imbalance observed during release testing of a small molecule API. The process followed a logical stepwise progression beginning with most probable causes and expanded to more obscure causes that require a deeper examination of the API in question until the undetected impurity in question was finally identified. The discovered impurity was eventually found to be formed from a unique side reaction that led to the formation of API-related oligomer impurities, which had eluded conventional small molecule release testing strategies. Ultimately, the characterization gap was traced back to deficiency in the LC results of the developed API purity methods. More importantly, this gap provides an ideal opportunity to highlight common oversights and pitfalls encountered in early phase pharmaceutical development especially as it relates to the method development of truly representative chromatography methods in the API characterization. The work reflects on the key lessons learned from the highlighted pitfalls that were encountered in this case study and offers strategic insights to guide and to improve the development workflow for drug substance characterization strategies.

In the pursuit of identifying the underlying pathways of ocular diseases, the use of cell lines such as (retinal ganglion cell-5) RGC-5 and 661W became a valuable tool, including pathologies like retinal degeneration and glaucoma. In 2001, the establishment of the RGC-5 cell line marked a significant breakthrough in glaucoma research. Over time, however, concerns arose about the true nature of RGC-5 cells, with conflicting findings in the literature regarding their identity as retinal ganglion cells or photoreceptor-like cells. This study aimed to address the controversy surrounding the RGC-5 cell line\'s origin and properties by comparing it with the 661W cell line, a known cone photoreceptor model. Both cell lines were differentiated according to two prior published redifferentiation protocols under the same conditions using 500 nM of trichostatin A (TSA) and investigated for their morphological and neuronal marker properties. The results demonstrated that both cell lines are murine, and they exhibited distinct morphological and neuronal marker properties. Notably, the RGC-5 cells showed higher expression of the neuronal marker β-III tubulin and increased Thy-1-mRNA compared with the 661W cells, providing evidence of their different properties. The findings emphasize the importance of verifying the authenticity of cell lines used in ocular research and highlight the risks of contamination and altered cell properties.

The unintentional consumption of fentanyl is a serious health risk for people who use illicit drugs. In an ongoing community-based study regarding polysubstance use among people who use opioids, we found that 17 of 58 (29%) of participants who did not endorse fentanyl use in the past thirty days tested positive for fentanyl during point-of-care urinalysis (UA). This paper describes the reactions and experiences of participants who were informed they had consumed fentanyl unintentionally, as well as how the research team handled the unanticipated occurrence of discordant results. Consistent with other recent studies, we found that people learning of unintentional fentanyl use expressed strong concerns about accidental overdose. It was common for participants to reflect on recent substance use experiences that were atypical and might have involved fentanyl, as well as to examine sources of recent drug purchases. While not all participants were surprised that they had unintentionally consumed fentanyl, all felt that learning their positive results was important due to risk of overdose. Research and medical staff have an opportunity to promote awareness of possible contamination by sharing and discussing UA test results with people who use drugs in non-judgmental manner. In addition to the widely promoted harm reduction strategy of testing drugs with fentanyl test strips, self-administered point-of-care UA, particularly after an unexpected reaction to using a drug, could provide useful information for people buying and using illicit drugs.

Air contamination in operating rooms (ORs) depends on the conditions of the room and on activities therein performed. Methodologies of air quality assessment in ORs are often inadequately described in the scientific literature, and the time required for a change in status in air quality is never taken into account. The purpose of this study was to determine the influence of the state and the presence of human operators on air quality by implementing a precise measurement protocol that also took into account the time required for changes in the room to affect air pollution. As the main indicators of air pollution, bacterial load and concentration of airborne dust were measured. The results showed that: the use of surgical masks by operators in the OR did not significantly affect bacterial load within a distance of 2 m; keeping OR doors open did not induce a significant increase in bacterial load and of 5 μm particles while 10 μm particles concentration was positively affected; and air pollution measured with open doors was not significantly different from that due to the presence of two staff members, whether or not they were wearing masks. The results clarified the role of some factors on air pollution in ORs.

A reverse phase high-performance liquid chromatography (HPLC) method has been developed for the quantification of a typical drug Dasatinib (DST) and its related impurities in pharmaceuticals. Kinetex C18 (4.6 × 150 mm, 5 μm) column was used in the chromatographic separations, using buffer (1.36 g of KH2PO4 in 1000 mL of water, pH = 7.8; adjusted with diluted KOH solution) with solvent as acetonitrile and mode of elution as the gradient. The flow rate is 0.9 mL/min, column oven temperature as 45°C and the overall gradient run time as 65 min. The developed method was found to produce symmetric and good separation between the process-related and degradation impurities. Method optimization is achieved with photodiode array at 305 nm over the concentration range of 0.5 mg/mL and degradation studies were carried out under acidic, alkaline, oxidative, photolytic and thermal conditions to demonstrate the stability indicating capability of the method. Two major impurities were found in forced degradation studies in the HPLC analysis, the unknown, acid degradants were enriched and isolated by preparative HPLC, then characterized through high-resolution mass spectrometry, nuclear magnetic resonance spectroscopy and Fourier transform infrared spectroscopy. The unknown acid degradation impurity was showing Exact Mass of 521.11, molecular formula C22H25Cl2N7O2S and its chemical name as 2-(5-chloro-6-(4-(2-hydroxyethyl) piperazin-1-yl)-2-methylpyrimidin-4-ylamino)-N-(2-chloro-6-methylphenyl) thiazole-5-carboxamide. Another impurity (oxidative degradant) found as known DST N-oxide Impurity-L and its chemical name as 4-(6-((5-((2-chloro-6-methylphenyl) carbamoyl) thiazol-2-yl) amino)-2-methylpyrimidin-4-yl)-1-(2-hydroxyethyl) piperazine 1-oxide. The analytical HPLC method was further validated as per ICH guidelines.