Meeting Report on the 2nd Chinese American Society for Mass Spectrometry Conference: Advancing Biological and Pharmaceutical Mass Spectrometry.

The 2nd CASMS conference was held virtually through Gather. Town platform from October 17 to 21, 2022, with a total of 363 registrants including an outstanding and diverse group of scientists at the forefront of their research fields from both academia and industry worldwide, especially in the United States and China. The conference offered a 5-day agenda with an exciting scientific program consisting of two plenary lectures, 14 parallel symposia, and 4 special sessions in which a total of 97 invited speakers presented technological innovations and their applications in proteomics & biological mass spectrometry and metabo-lipidomics & pharmaceutical mass spectrometry. In addition, 18 invited speakers/panelists presented at 3 research-focused and 2 career development workshops. Moreover, 144 posters, 54 lightning talks, 5 sponsored workshops, and 14 exhibitions were presented, from which 20 posters and 8 lightning talks received presentation awards. Furthermore, the conference featured 1 MCP lectureship and 5 young investigator awardees for the first time to highlight outstanding mid-career and early-career rising stars in mass spectrometry from our society. The conference provided a unique scientific platform for young scientists (i.e., graduate students, postdocs and junior faculty/investigators) to present their research, meet with prominent scientists, and learn about career development and job opportunities (http://casms.org).

A Compensation Method for the Geomagnetic Measurement Error of an Underwater Ship-Borne Magnetometer Based on Constrained Total Least Squares.

When magnetic matching aided navigation is applied to an underwater vehicle, the magnetometer must be installed inside the vehicle, considering the navigation safety and concealment of the underwater vehicle. Then, the interference magnetic field will seriously affect the accuracy of geomagnetic field measurement, which directly affects the accuracy of geomagnetic matching aided navigation. Therefore, improving the accuracy of geomagnetic measurements inside the vehicle through error compensation has become one of the most difficult problems that requires an urgent solution in geomagnetic matching aided navigation. In order to solve this problem, this paper establishes the calculation model of the internal magnetic field of the underwater vehicle and the geomagnetic measurement error model of the ship-borne magnetometer. Then, a compensation method for the geomagnetic measurement error of the ship-borne magnetometer, based on the constrained total least square method, is proposed. To verify the effectiveness of the method proposed in this paper, a simulation experiment of geomagnetic measurement and compensation of a ship-borne three-axis magnetometer was constructed. Among them, to be closer to the real situation, a combination of the geomagnetism model, the elliptic shell model and the magnetic dipole model was used to simulate the internal magnetic field of the underwater vehicle. The experimental results indicated that the root mean square error of geomagnetic measurement in an underwater vehicle was less than 5 nT after compensation, and the accuracy of geomagnetic measurement met the requirements of geomagnetic matching aided navigation.

LC-MS/MS Bioanalysis of Radioligand Therapeutic Drug Candidate for Preclinical Toxicokinetic Assessment.

Radioligand therapy (RLT) has gained significant momentum in recent years in the diagnosis, treatment, and monitoring of cancers. In preclinical development, the safety profile of RLT drug candidate(s) is investigated at relatively low dose levels using the cold (non-radioactive, e.g., 175Lu) ligand as a surrogate of the hot (radioactive, e.g., 177Lu) one in the "ligand-linker-chelator" complex. The formulation of the test article used in preclinical safety studies contains a mixture of free ligand (i.e., ligand-linker-chelator without metal) and cold ligand (i.e., ligand-linker-chelator with non-radioactive metal) in a similar molar ratio as seen under the manufacturing conditions for the RLT drug for clinical use, where only a fraction of free ligand molecules chelate the radioactive metal to form a hot ligand. In this very first report of LC-MS/MS bioanalysis of RLT molecules in support of a regulated preclinical safety assessment study, a highly selective and sensitive LC-MS/MS bioanalytical method was developed for the simultaneous determination of free ligand (NVS001) and cold ligand (175Lu-NVS001) in rat and dog plasma. Several unexpected technical challenges in relation to LC-MS/MS of RLT molecules were successfully addressed. The challenges include poor assay sensitivity of the free ligand NVS001, formation of the free ligand (NVS001) with endogenous metal (e.g., potassium), Ga loss from the Ga-chelated internal standard during sample extraction and analysis, "instability" of the analytes at low concentrations, and inconsistent IS response in the extracted plasma samples. The methods were validated according to the current regulatory requirements in a dynamic range of 0.5-250 ng/mL for both the free and cold ligands using a 25 µL sample volume. The validated method was successfully implemented in sample analysis in support of regulated safety studies, with very good results from incurred sample reanalysis. The current LC-MS/MS workflow can be expanded to quantitative analysis of other RLTs in support of preclinical RLT drug development.

Toxicokinetics in preclinical drug development of small-molecule new chemical entities.

Toxicokinetics (TK) is an integral part of nonclinical (preclinical) safety assessment of small-molecule new chemical entities in drug development. It is employed to describe the systemic exposure of a drug candidate and/or its important metabolite(s) achieved in study animals and elucidate the relationship (proportional, over-proportional, or under-proportional) between systemic exposure and dose administered and the associated differences/similarities between male and female animals along with the possible accumulation/induction. TK data and the derived parameters are employed to propose safe starting doses for clinical use of the new drug candidate through proper extrapolation of findings in study animals to humans. This review has attempted to highlight the health authority expectations on TK assessment in supporting preclinical safety profiling of new chemical entities. A robust TK assessment requires good understanding of absorption, distribution, metabolism, and elimination processes of drug candidate, adequate TK sampling (e.g., controls where relevant), implementation of fit-for-purpose bioanalytical methods (validated or scientifically qualified) along with necessary measures to prevent mis-dosing or ex vivo contamination, and establishment of stability of the drug candidate and/or its metabolite(s) in the intended species matrix to ensure the reliability of bioanalytical and TK data. The latter provides a vital link between animal experiments and human safety.

Long noncoding RNA HAS2-AS1 promotes tumor progression in glioblastoma via functioning as a competing endogenous RNA.

Glioblastoma multiforme (GBM) is a refractory tumor with poor prognosis and requires more effective treatment regimens. It has been confirmed that long noncoding RNAs (lncRNAs) substantially regulate various human disease including GBM. However, the biological roles and its underlying molecular mechanisms still need to be further investigated. In this study, the biological function and potential molecular mechanism of lncHAS2-AS1 in GBM were explored. It was discovered that HAS2-AS1 was elevated in glioma tissues and correlated with the prognosis of patients with glioma. Reduction of HAS2-AS1 suppressed the migration and invasion in vitro and in vivo. The transcription factor STAT1 could raise HAS2-AS1 by binding to its promoter region. Besides, HAS2-AS1 could adjust PRPS1 via sponging miR-608 in a direct manner. On the whole, the results of this study evidence that HAS2-AS1 is an oncogene and a potential therapeutic target for GBM.

Postcardiac injury syndrome, peripheral hematoma of ascending aorta, and cerebral infarction after PCI: a case report.

BACKGROUND: Postcardiac injury syndrome (PCIS) is an inflammatory response syndrome characterized by pericardial effusion with or without pleural effusion; however, serious PCIS with peripheral hematoma of the ascending aorta and acute cerebral infarction after percutaneous coronary intervention (PCI) have not been reported. CASE PRESENTATION: This article reports a very rare case of a 40-year-old patient who developed acute pericardial and pleural effusions (both bloody), acute respiratory distress, peripheral hematoma of the ascending aorta, and acute cerebral infarction after PCI. The patient's ECG showed bow-back downward ST elevation in leads I, II, III, and V4-V6. A blood test showed significant increases in eukaryotic-cell count, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP). Echocardiography and pulmonary artery computed tomography angiography (CTA) showed a large amount of pericardial effusion and pleural effusion. CTA of the thoracic and abdominal aorta showed a peripheral hematoma of the ascending aorta. A cranial computed tomography (CT) showed cerebral infarction anterior to the anterior horn of the right ventricle. After tracheal intubation, ventilator breathing support, pericardial and pleural drainage, and adrenocortical steroid (prednisone) treatment, he gradually recovered and was discharged 20 days later. CONCLUSION: We report the management of a case of serious PCIS with peripheral hematoma of the ascending aorta and acute cerebral infarction after PCI. Early diagnosis, early differential diagnosis, and early use of steroid therapy are the key in treating PCIS.

Application of tail vein serial microsampling for plasma or dried plasma spots in toxicokinetic assessment in rats using acetaminophen as the model compound.

In the current study, two groups of rats (five per group) were administered a single oral dose of 500 mg/kg acetaminophen. For toxicokinetic assessment, the Group 1 animals were bled via conventional sparse (two animals/time point) sublingual vein bleeding (~0.5 ml) with anesthesia, while the Group 2 animals were bled via serial tail vein microsampling (~0.075 ml) without anesthesia. All collected blood was processed for plasma. Each Group 2 plasma sample (~30 µl) was divided into 'wet' and 'dried' (dried plasma spots). All plasma samples were analyzed by LC-MS/MS for acetaminophen and its major metabolites acetaminophen glucuronide and acetaminophen sulfate. In addition, plasma and urine samples were collected for analysis of corticosterone and creatinine to assess stress levels. Comparable plasma exposure to acetaminophen and its two metabolites was observed in the plasma obtained via conventional sparse sublingual vein bleeding and serial tail vein microsampling and between the 'wet' and 'dried' plasma obtained by the latter. Furthermore, comparable corticosterone levels or corticosterone/creatinine ratios between the two groups suggested that serial microsampling without anesthesia did not increase the levels of stress as compared with conventional sampling with anesthesia, confirming the utility of microsampling for plasma or dried plasma spots in rodent toxicokinetic assessment.

Metabolism and Disposition of Siponimod, a Novel Selective S1P1/S1P5 Agonist, in Healthy Volunteers and In Vitro Identification of Human Cytochrome P450 Enzymes Involved in Its Oxidative Metabolism.

Siponimod, a next-generation selective sphingosine-1-phosphate receptor modulator, is currently being investigated for the treatment of secondary progressive multiple sclerosis. We investigated the absorption, distribution, metabolism, and excretion (ADME) of a single 10-mg oral dose of [14C]siponimod in four healthy men. Mass balance, blood and plasma radioactivity, and plasma siponimod concentrations were measured. Metabolite profiles were determined in plasma, urine, and feces. Metabolite structures were elucidated using mass spectrometry and comparison with reference compounds. Unchanged siponimod accounted for 57% of the total plasma radioactivity (area under the concentration-time curve), indicating substantial exposure to metabolites. Siponimod showed medium to slow absorption (median Tmax: 4 hours) and moderate distribution (Vz/F: 291 l). Siponimod was mainly cleared through biotransformation, predominantly by oxidative metabolism. The mean apparent elimination half-life of siponimod in plasma was 56.6 hours. Siponimod was excreted mostly in feces in the form of oxidative metabolites. The excretion of radioactivity was close to complete after 13 days. Based on the metabolite patterns, a phase II metabolite (M3) formed by glucuronidation of hydroxylated siponimod was the main circulating metabolite in plasma. However, in subsequent mouse ADME and clinical pharmacokinetic studies, a long-lived nonpolar metabolite (M17, cholesterol ester of siponimod) was identified as the most prominent systemic metabolite. We further conducted in vitro experiments to investigate the enzymes responsible for the oxidative metabolism of siponimod. The selective inhibitor and recombinant enzyme results identified cytochrome P450 2C9 (CYP2C9) as the predominant contributor to the human liver microsomal biotransformation of siponimod, with minor contributions from CYP3A4 and other cytochrome P450 enzymes.

Quantitative analysis of clofazimine (Lamprene®), an antileprosy agent, in human dried blood spots using liquid chromatography-tandem mass spectrometry.

An LC-MS/MS method was developed and validated for bioanalysis of clofazimine in human dried blood spot (DBS) samples in support of a clinical study on multidrug-resistant tuberculosis in developing countries. The validated assay dynamic range was from 10.0 to 2000 ng/mL using a 1/8 inch DBS punch. The accuracy and precision of the assay were ±11.0% (bias) and ≤13.5% (CV) for the LLOQs (10.0 ng/mL) and ±15% (bias) and ≤15% (CV) for all other QC levels. The assay was proved to be free from the possible impact owing to spot size and storage temperature (e.g. at 60°C, ≤ - 60°C). The validated assay is well suited for the intended clinical study where conventional pharmacokinetic sample collection is not feasible.

Differential Mobility Spectrometry Coupled with Multiple Ion Monitoring in Regulated LC-MS/MS Bioanalysis of a Therapeutic Cyclic Peptide in Human Plasma.

A differential mobility spectrometry (DMS) in combination with a multiple ion monitoring (MIM) method was developed and validated for quantitative LC-MS/MS bioanalysis of pasireotide (SOM230) in human plasma. Pasireotide, a therapeutic cyclic peptide, exhibits poor collision-induced dissociation (CID) efficiency for multiple reaction monitoring (MRM) detection. Therefore, in an effort to increase the overall sensitivity of the assay, a DMS-MIM approach was explored. By selecting the most abundant doubly charged precursor ion in both the Q1 and Q3 of the mass analyzer in MIM and combining the DMS capability to significantly reduce the high matrix/chemical background noise, this new LC-DMS-MIM method overcomes the sensitivity challenge in the typical MRM method due to poor CID fragmentation of the analyte. Human plasma was spiked with pasireotide with concentrations in the range 0.01-50 ng/mL. Weak cation-exchange solid-phase extraction was employed for sample preparation. The sample extracts were analyzed with a SCIEX QTRAP 6500 system equipped with an ESI source and DMS device. The separation voltage and compensation voltage of the DMS and other parameters of the MS system were optimized to maximize signal responses. The performance of the LC-DMS-MIM assay for quantitative analysis of pasireotide in human plasma was evaluated and compared to those obtained via LC-MRM and LC-MIM without DMS. Overall, the assay sensitivity with DMS-MIM was approximately 5-fold better than that observed in MRM or MIM without DMS. The assay was validated with accuracy (% bias) and precision (% CV) of the QC results at eight concentration levels (0.01, 0.02, 0.05, 0.15, 0.3, 1.5, 15, and 37.5 ng/mL) evaluated ranging from -4.8 to 5.0% bias and 0.7 to 8.6% CV for the intraday and interday runs. The current LC-DMS-MIM workflow can be expanded to quantitative analysis of other molecules that have poor fragmentation efficiency in CID.

Naphthoquine-induced Central Nervous System and Hepatic Vasculocentric Toxicity in the Beagle Dog.

Naphthoquine phosphate (NP) was considered as a partner drug with a promising antimalarial drug candidate. Here we report unexpected adverse clinical signs and microscopic findings in a canine pilot toxicology study with NP. Male and female dogs were dosed daily by oral gavage with NP at 2, 10, or 50 mg/kg/day for a maximum of 14 days. NP was not tolerated at ≥10 mg/kg/day; several animals were sacrificed in moribund condition and marked neurological clinical signs were noted at 50 mg/kg/day. The main microscopic observation was central nervous system vasculocentric inflammation (mainly lymphocytes and macrophages) in the white and gray matter of various regions of the brain at ≥2 mg/kg/day and at lower incidence in the spinal cord at ≥10 mg/kg/day. Vasculocentric microscopic changes predominantly centered on the centrilobular vein were also observed in the liver at ≥2 mg/kg/day. Females were more sensitive than males with comparable NP plasma exposure. In conclusion, under the conditions of this study, the administration of NP to dogs via daily oral gavage for up to 2 weeks was not tolerated causing moribundity, marked neurological clinical signs, and vasculocentric microscopic changes in the central nervous system and the liver.

Osilodrostat (LCI699), a potent 11ß-hydroxylase inhibitor, administered in combination with the multireceptor-targeted somatostatin analog pasireotide: A 13-week study in rats.

The somatostatin analog pasireotide and the 11ß-hydroxylase inhibitor osilodrostat (LCI699) reduce cortisol levels by distinct mechanisms of action. There exists a scientific rationale to investigate the clinical efficacy of these two agents in combination. This manuscript reports the results of a toxicology study in rats, evaluating different doses of osilodrostat and pasireotide alone and in combination. Sixty male and 60 female rats were randomized into single-sex groups to receive daily doses of pasireotide (0.3mg/kg/day, subcutaneously), osilodrostat (20mg/kg/day, orally), osilodrostat/pasireotide in combination (low dose, 1.5/0.03mg/kg/day; mid-dose, 5/0.1mg/kg/day; or high dose, 20/0.3mg/kg/day), or vehicle for 13weeks. Mean body-weight gains from baseline to Week 13 were significantly lower in the pasireotide-alone and combined-treatment groups compared to controls, and were significantly higher in female rats receiving osilodrostat monotherapy. Osilodrostat and pasireotide monotherapies were associated with significant changes in the histology and mean weights of the pituitary and adrenal glands, liver, and ovary/oviduct. Osilodrostat alone was associated with adrenocortical hypertrophy and hepatocellular hypertrophy. In combination, osilodrostat/pasireotide did not exacerbate any target organ changes and ameliorated the liver and adrenal gland changes observed with monotherapy. Cmax and AUC0-24h of osilodrostat and pasireotide increased in an approximately dose-proportional manner. In conclusion, the pasireotide and osilodrostat combination did not exacerbate changes in target organ weight or toxicity compared with either monotherapy, and had an acceptable safety profile; addition of pasireotide to the osilodrostat regimen may attenuate potential adrenal gland hyperactivation and hepatocellular hypertrophy, which are potential side effects of osilodrostat monotherapy.

Comparison of Perioperative Safety of Carotid Artery Stenting and Endarterectomy in the Treatment of Carotid Artery Stenosis: A Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Current management guidelines for the treatment of carotid stenosis are controversial. We performed this meta-analysis to evaluate the perioperative safety of carotid artery stenting (CAS) and endarterectomy. METHODS: We systematically searched EMBASE, PubMed, Web of Science, and the Cochrane Library from inception to November 10, 2022, for randomized controlled trials that compared CAS with carotid endarterectomy (CEA) among patients with carotid stenosis. The analyzed outcomes mainly included stroke, death, myocardial infarction (MI), cranial nerve palsy, the cumulative incidence of mortality, stroke, or MI and the cumulative incidence of death or stroke in the perioperative periods. The risk ratio (RR) and 95% confidence interval (95% CI) were calculated and pooled. Subgroup analyses were based on whether patients were symptomatic or asymptomatic. We assessed the certainty of evidence using the Grading of Recommendations Assessment, Development and Evaluation framework. RESULTS: Seventeen randomized controlled trials with 12,277 participants (6514 and 5763 in the CAS and CEA groups, respectively) were included. Pooled analysis demonstrated that compared with CEA, CAS was associated with decreased risks of perioperative MI (RR = 0.47, 95% CI = 0.29∼0.77) and perioperative cranial nerve palsy (RR = 0.02, 95% CI = 0.01∼0.06) but higher risks of perioperative stroke (RR = 1.48, 95% CI = 1.18∼1.87) and cumulative incidence of death or stroke (RR = 1.52, 95% CI = 1.20∼1.93). CONCLUSIONS: The perioperative safety was equivalent between CAS and CEA. However, CEA may be preferred when considering both procedural safety and long-term efficacy in preventing recurrent stroke.

Discovery of Novel Cinnamic Acid Derivatives as Fungicide Candidates.

Structural diversity derivatization from natural products is an important and effective method of discovering novel green pesticides. Cinnamic acids are abundant in plants, and their unparalleled structures endow them with various excellent biological activities. A series of novel cinnamic oxime esters were designed and synthesized to develop high antifungal agrochemicals. The antifungal activity, structure-activity relationship, and action mechanism were systematically studied. Compounds 7i, 7u, 7v, and 7x exhibited satisfactory activity against Gaeumannomyces graminis var. tritici, with inhibition rates of ≥90% at 50 µg/mL. Compounds 7z and 7n demonstrated excellent activities against Valsa mali and Botrytis cinerea, with median effective concentration (EC50) values of 0.71 and 1.41 µg/mL, respectively. Compound 7z exhibited 100% protective and curative activities against apple Valsa canker at 200 µg/mL. The control effects of 7n against gray mold on tomato fruits and leaves were all >96%, exhibiting superior or similar effects to those of the commercial fungicide boscalid. Furthermore, the quantitative structure-activity relationship was established to guide the further design of higher-activity compounds. The preliminary results on the action mechanism revealed that 7n treatment could disrupt the function of the nucleus and mitochondria, leading to reactive oxygen species accumulation and cell membrane damage. Its primary biochemical mechanism may be inhibiting fungal ergosterol biosynthesis. The novel structure, simple synthesis, and excellent activity of cinnamic oxime esters render them promising potential fungicides.

Efficacy and toxic action of the natural product natamycin against Sclerotinia sclerotiorum.

BACKGROUND: Sclerotinia stem rot caused by Sclerotinia sclerotiorum seriously endangers oilseed rape production worldwide, and the occurrence of fungicide-resistant mutants of S. sclerotiorum leads to control decline. Thus, it is critical to explore new green substitutes with different action mechanisms and high antifungal activity. Herein, the activity and the action mechanism of natamycin against S. sclerotiorum were evaluated. RESULTS: Natamycin showed potent inhibition on the mycelial growth of S. sclerotiorum, and half-maximal effective concentration (EC50 ) values against 103 S. sclerotiorum strains ranged from 0.53 to 4.04 µg/mL (mean 1.44 µg/mL). Natamycin also exhibited high efficacy against both carbendazim- and dimethachlone-resistant strains of S. sclerotiorum on detached oilseed rape leaves. No cross-resistance was detected between natamycin and carbendazim. Natamycin markedly disrupted hyphal form, sclerotia formation, integrity of the cell membrane, and reduced the content of oxalic acid and ergosterol, whereas it increased the reactive oxygen species (ROS) and malondialdehyde content. Interestingly, exogenous addition of ergosterol could reduce the inhibition of natamycin against S. sclerotiorum. Importantly, natamycin significantly inhibited expression of the Cyp51 gene, which is contrary to results for the triazole fungicide flusilazole, indicating a different action mechanism from triazole fungicides. CONCLUSION: Natamycin is a promising effective candidate for the resistance management of S. sclerotiorum. © 2023 Society of Chemical Industry.

Metabolite Bioanalysis in Drug Development: Recommendations from the IQ Consortium Metabolite Bioanalysis Working Group.

The intent of this perspective is to share the recommendations of the International Consortium for Innovation and Quality in Pharmaceutical Development Metabolite Bioanalysis Working Group on the fit-for-purpose metabolite bioanalysis in support of drug development and registration. This report summarizes the considerations for the trigger, timing, and rigor of bioanalysis in the various assessments to address unique challenges due to metabolites, with respect to efficacy and safety, which may arise during drug development from investigational new drug (IND) enabling studies, and phase I, phase II, and phase III clinical trials to regulatory submission. The recommended approaches ensure that important drug metabolites are identified in a timely manner and properly characterized for efficient drug development.

Practical approaches to incurred sample LC-MS/MS reanalysis: confirming unexpected results.

Incurred sample reanalysis (ISR) is an important step in assuring the quality of an LC-MS/MS bioanalytical assay and the integrity of bioanalysis conduct. A conventional ISR involves analysis of at least 20 samples taken from an in vivo study a second time using the method that was described in prestudy validation and employed in generating the initial study sample results. However, this practice is sometimes inadequate to confirm bioanalytical results that are unexpected. The present report discusses several additional exploratory activities that were performed to confirm the unexpected plasma concentration-time results of NVP-1, an investigational drug candidate, observed in the plasma samples collected from patients in a phase II trial. These approaches include (1) LC-MS/MS reanalysis of the study samples after multiple freeze/thaw cycles followed by a short-term benchtop storage, (2) evaluation of additional MS/MS transitions in LC-MS/MS, (3) employment of a different sample preparation procedure in LC-MS/MS, and (4) study sample dilution using plasma samples from healthy volunteers. These procedures are practical and can be readily implemented in the confirmatory LC-MS/MS bioanalysis of other small molecules.

Non-regulated LC-MS/MS bioanalysis in support of early drug development: a Novartis perspective.

Scientifically qualified LC-MS/MS methods are essential for the determination of small molecule drug candidates and/or their metabolite(s) in support of various non-regulated safety assessment and in vivo absorption, distribution, metabolism and excretion studies in preclinical development. This article outlines an effective method development workflow to fit for this purpose. The workflow features a 'universal' protein precipitation solvent for efficient sample extraction, a mobile phase additive for managing chromatographic resolution and addressing carryover and an internal standard cocktail to select the best analogue internal standard to track the analyte of interest in LC-MS/MS. In addition, good practices are recommended to prevent bioanalytical pitfalls due to instability, non-specific binding and dosing vehicle-induced matrix effect. Proper handling of non-liquid matrix is also discussed.

Matrine can be absorbed and transmitted bidirectionally to defend against aphids (Hemiptera: Aphididae) on wheat and pepper.

BACKGROUND: Although matrine is widely used, its absorption and transport mechanisms in crops remain unexplored. In this study, three methods including foliar application, hydroponics and seed immersion were used to investigate whether matrine molecules could enter into plants through different channels, and to further resolve its transport characteristics. The systemic activity of matrine also was evaluated. RESULT: Matrine was quickly absorbed and transported downwards after the leaves of wheat or peppers were treated, and also accumulated and transmitted upwards by roots. It was not only absorbed by seeds, but also appeared continuously in young roots and leaves in both plants for nearly 20 days. There were some differences in the uptake and conduction of matrine between pepper and wheat: matrine concentrated in pepper upper leaves with less delivered downwards to roots than in wheat, and also transduction of matrine in pepper lower leaves upwards to upper leaves was less than in wheat. Matrine had systemic activity, with LC50 of 361.99 and 904.24 µg·mL-1 against Rhopalosiphum padib on wheat and Myzus persicae (Sulzer) on pepper plants at 48 h, separately. CONCLUSION: Matrine can be absorbed by the roots, seeds and leaves of plants, and transmitted bidirectionally to any organs, presenting satisfactory systemic poisoning activity against aphids. It is of great significance to develop new formulation products of matrine and promote its commercialized value. © 2023 Society of Chemical Industry.

2022 White Paper on Recent Issues in Bioanalysis: ICH M10 BMV Guideline & Global Harmonization; Hybrid Assays; Oligonucleotides & ADC; Non-Liquid & Rare Matrices; Regulatory Inputs (Part 1A - Recommendations on Mass Spectrometry, Chromatography and Sample Preparation, Novel Technologies, Novel Modalities, and Novel Challenges, ICH M10 BMV Guideline & Global Harmonization Part 1B - Regulatory Agencies' Inputs on Regulated Bioanalysis/BMV, Biomarkers/CDx/BAV, Immunogenicity, Gene & Cell Therapy and Vaccine).

The 16th Workshop on Recent Issues in Bioanalysis (16th WRIB) took place in Atlanta, GA, USA on September 26-30, 2022. Over 1000 professionals representing pharma/biotech companies, CROs, and multiple regulatory agencies convened to actively discuss the most current topics of interest in bioanalysis. The 16th WRIB included 3 Main Workshops and 7 Specialized Workshops that together spanned 1 week in order to allow exhaustive and thorough coverage of all major issues in bioanalysis, biomarkers, immunogenicity, gene therapy, cell therapy and vaccines. Moreover, in-depth workshops on the ICH M10 BMV final guideline (focused on this guideline training, interpretation, adoption and transition); mass spectrometry innovation (focused on novel technologies, novel modalities, and novel challenges); and flow cytometry bioanalysis (rising of the 3rd most common/important technology in bioanalytical labs) were the special features of the 16th edition. As in previous years, WRIB continued to gather a wide diversity of international, industry opinion leaders and regulatory authority experts working on both small and large molecules as well as gene, cell therapies and vaccines to facilitate sharing and discussions focused on improving quality, increasing regulatory compliance, and achieving scientific excellence on bioanalytical issues. This 2022 White Paper encompasses recommendations emerging from the extensive discussions held during the workshop and is aimed to provide the bioanalytical community with key information and practical solutions on topics and issues addressed, in an effort to enable advances in scientific excellence, improved quality and better regulatory compliance. Due to its length, the 2022 edition of this comprehensive White Paper has been divided into three parts for editorial reasons. This publication (Part 1A) covers the recommendations on Mass Spectrometry and ICH M10. Part 1B covers the Regulatory Agencies' Inputs on Bioanalysis, Biomarkers, Immunogenicity, Gene & Cell Therapy and Vaccine. Part 2 (LBA, Biomarkers/CDx and Cytometry) and Part 3 (Gene Therapy, Cell therapy, Vaccines and Biotherapeutics Immunogenicity) are published in volume 15 of Bioanalysis, issues 15 and 14 (2023), respectively.