[Determination of multiple residual solvents in ibandronate sodium using headspace-gas chromatography].

Ibandronate sodium, a third-generation diphosphate drug used worldwide to treat osteoporosis, has the advantages of convenient use, low toxicity, and significant therapeutic effects. However, the residual organic solvents in the synthesis process of sodium ibandronate not only have a negative impact on the efficacy of the drug, but also lead to a decrease in drug stability. Moreover, if the residual amounts of these solvents exceed safety standards, they may pose serious threats to human health. This study successfully established a convenient and efficient method based on headspace-gas chromatography (HS-GC) for the simultaneous determination of five residual solvents (methanol, acetone, benzene, toluene, 1-pentanol) in the raw materials of ibandronate sodium. The results indicated that satisfactory analytical performance can be achieved by using DB-624 capillary column (30 m×0.32 mm×1.8 µm) and a flame ionization detector in conjunction with headspace autosampling and a temperature program. The specific operating conditions included an initial temperature of 40 ℃, with a hold of 2 min, followed by a temperature ramp first to 200 ℃ at a rate of 5 ℃/min and then to 240 ℃ at a rate of 20 ℃/min, with a hold of 5 min. Nitrogen with a flow rate of 1 mL/min and split ratio of 14∶1 was used as the carrier gas. The headspace vial temperature was maintained at 80 ℃, and the sample equilibration time was 20 min. Under the established analytical conditions, good linear relationships were obtained between the mass concentrations of methanol (72-216 µg/mL), acetone (120-360 µg/mL), benzene (0.048-0.144 µg/mL), toluene (21.36-64.08 µg/mL), and 1-pentanol (120-360 µg/mL) and their corresponding peak areas, with correlation coefficients (r) greater than 0.990. The limits of detection for these solvents were 2.88, 0.011, 0.90, 0.24, and 0.024 ng/mL, respectively, with limits of quantification of 11.5, 0.043, 3.6, 0.96, and 0.096 ng/mL, respectively. Furthermore, the recoveries of these solvents ranged from 86.3% to 101.9%, with relative standard deviations (RSDs, n=3) of less than 2.49%. The proposed method is simple, accurate, reliable, and suitable for the rapid and simultaneous determination of five residual solvents in the raw materials of ibandronate sodium. This study has important practical significance in improving drug safety and ensuring public health.

Deep eutectic solvents as green and sustainable diluents in headspace gas chromatography for the determination of trace level genotoxic impurities in pharmaceuticals.

Genotoxic impurities (GTIs) are potential carcinogens that need to be controlled down to ppm or lower concentration levels in pharmaceuticals under strict regulations. The static headspace gas chromatography (HS-GC) coupled with electron capture detection (ECD) is an effective approach to monitor halogenated and nitroaromatic genotoxins. Deep eutectic solvents (DESs) possess tunable physico-chemical properties and low vapor pressure for HS-GC methods. In this study, zwitterionic and non-ionic DESs have been used for the first time to develop and validate a sensitive analytical method for the analysis of 24 genotoxins at sub-ppm concentrations. Compared to non-ionic diluents, zwitterionic DESs produced exceptional analytical performance and the betaine : 7 (1,4- butane diol) DES outperformed the betaine : 5 (1,4-butane diol) DES. Limits of detection (LOD) down to the 5-ppb concentration level were achieved in DESs. Wide linear ranges spanning over 5 orders of magnitude (0.005-100 µg g-1) were obtained for most analytes with exceptional sensitivities and high precision. The method accuracy and precision were validated using 3 commercially available drug substances and excellent recoveries were obtained. This study broadens the applicability of HS-GC in the determination of less volatile GTIs by establishing DESs as viable diluent substitutes for organic solvents in routine pharmaceutical analysis.

Assessing biologic/toxicologic effects of extractables from plastic contact materials for advanced therapy manufacturing using cell painting assay and cytotoxicity screening.

Plastic components are essential in the pharmaceutical industry, encompassing container closure systems, laboratory handling equipment, and single-use systems. As part of their material qualification process, studies on interactions between plastic contact materials and process solutions or drug products are conducted. The assessment of single-use systems includes their potential impact on patient safety, product quality, and process performance. This is particularly crucial in cell and gene therapy applications since interactions with the plastic contact material may result in an adverse effect on the isolated therapeutic human cells. We utilized the cell painting assay (CPA), a non-targeted method, for profiling the morphological characteristics of U2OS human osteosarcoma cells in contact with chemicals related to plastic contact materials. Specifically, we conducted a comprehensive analysis of 45 common plastic extractables, and two extracts from single-use systems. Results of the CPA are compared with a standard cytotoxicity assay, an osteogenesis differentiation assay, and in silico toxicity predictions. The findings of this feasibility study demonstrate that the device extracts and most of the tested compounds do not evoke any measurable biological changes on the cells (induction ≤ 5%) among the 579 cell features measured at concentrations ≤ 50 µM. CPA can serve as an important assay to reveal unique information not accessible through quantitative structure-activity relationship analysis and vice versa. The results highlight the need for a combination of in vitro and in silico methods in a comprehensive assessment of single-use equipment utilized in advanced therapy medicinal products manufacturing.

Comprehensive Impurity Profiling of mRNA: Evaluating Current Technologies and Advanced Analytical Techniques.

In vitro transcription (IVT) of mRNA is a versatile platform for a broad range of biotechnological applications. Its rapid, scalable, and cost-effective production makes it a compelling choice for the development of mRNA-based cancer therapies and vaccines against infectious diseases. The impurities generated during mRNA production can potentially impact the safety and efficacy of mRNA therapeutics, but their structural complexity has not been investigated in detail yet. This study pioneers a comprehensive profiling of IVT mRNA impurities, integrating current technologies with innovative analytical tools. We have developed highly reproducible, efficient, and stability-indicating ion-pair reversed-phase liquid chromatography and capillary gel electrophoresis methods to determine the purity of mRNA from different suppliers. Furthermore, we introduced the applicability of microcapillary electrophoresis for high-throughput (<1.5 min analysis time per sample) mRNA impurity profiling. Our findings revealed that impurities are mainly attributed to mRNA variants with different poly(A) tail lengths due to aborted additions or partial hydrolysis and the presence of double-stranded mRNA (dsRNA) byproducts, particularly the dsRNA 3'-loop back form. We also implemented mass photometry and native mass spectrometry for the characterization of mRNA and its related product impurities. Mass photometry enabled the determination of the number of nucleotides of different mRNAs with high accuracy as well as the detection of their size variants [i.e., aggregates and partial and/or total absence of the poly(A) tail], thus providing valuable information on mRNA identity and integrity. In addition, native mass spectrometry provided insights into mRNA intact mass, heterogeneity, and important sequence features such as poly(A) tail length and distribution. This study highlights the existing bottlenecks and opportunities for improvement in the analytical characterization of IVT mRNA, thus contributing to the refinement and streamlining of mRNA production, paving the way for continued advancements in biotechnological applications.

Qualitative and quantitative analysis of glutathione and related impurities in pharmaceuticals by qNMR.

In this study, an alternative method to compendial analytical procedures with enhanced detection and separation capabilities was validated for the quality assessment of glutathione (GSH) drug substance. The related impurities A, B, C, and D present in GSH drug substance were characterized using a one-dimension proton nuclear magnetic resonance (1D 1H NMR) method on a 600 MHz spectrometer equipped with a liquid nitrogen cryoprobe. Two sample preparations at different pH were optimized to ensure the unambiguous identification of different impurities in the GSH samples. Specifically, impurities A and C in a GSH sample can be tested at pH 3.0, while pH 7.4 is more suitable for testing impurities B and D. The quantitative NMR (qNMR) method was validated following International Council for Harmonisation (ICH) guidelines. The limit of detection (LOD) was less than 0.1% wt for an individual impurity, and the limit of quantitation (LOQ) ranged from 0.14 to 0.24% wt, using about 14 min experimental time per spectrum. Following validation, the qNMR method was applied to assess different commercial GSH bulk substance samples, an in-house compounded GSH drug product, and a GSH dietary supplement product. The method was also applied to monitor GSH degradation (hydrolysis and oxidation) over time to provide quantitative information on GSH degradation and stability. The results suggest that the qNMR method can serve as a highly specific and efficient orthogonal tool for assessing the quality of GSH pharmaceuticals, providing both qualitative and quantitative information on GSH and its related impurities A-D.

Eco-Friendly Stability-Indicating HPLC Method for Related Compounds in Pemetrexed Ditromethamine (Antineoplastic Agent) for Injection.

BACKGROUND: An eco-friendly analytical technique was developed with the intention of preserving the environment by using green chemistry principles. Pemetrexed is a folate analogue indicated for the treatment of advanced lung cancer. OBJECTIVE: Development of a green stability-indicating HPLC method for the quantification of pemetrexed ditromethamine (PDT) impurities in Active Pharmaceutical Ingredient (API) and parenteral dosage form. METHODS: Chromatographic separation was achieved using a Zorbax SB C18 column (150 mm × 4.6 mm i.d., 3.5 µ particle size) with perchlorate buffer (pH 3.0 ± 0.1, 50 mM) as mobile phase A and acetonitrile-perchlorate (90 + 10, v/v) buffer as mobile phase B at a flow rate of 0.8 mL/min with a column temperature of 40°C ± 0.5°C. All analytes were well resolved by gradient elution with a total run time of 75 min. The UV detection wavelength was 230 nm. RESULTS: The RP-HPLC method is capable of resolving all the degradation and process impurities for PDT API and parenteral dosage form. The related compounds method was validated in accordance with International conference on harmonization (ICH) Q2(R1) and United states of Pharmacopoeia (USP) <1225> guidelines, and found to be accurate, specific, precise, linear, robust and stability-indicating. The precision and intermediate results were <5% CV for all the impurities. The accuracy for all the impurities was found to be between 90 and 110%. The linearity of regression co-efficient values for all the impurities were found to be more than 0.999. CONCLUSION: The proposed related compounds method is found suitable for the determination of process and degradation impurities of commercial formulations, stability samples in QC analysis for PDT API, and drug product. HIGHLIGHTS: The developed liquid chromatographic method greenness and eco-friendliness were assessed using the green analytical procedure index (GAPI) and the analytical greenness (AGREE) tool, and found to be green. A PDT detoxification procedure was also developed to reduce environmental pollution.

A new ultrasound-assisted microextraction for elemental impurities determination in tablets by ICP-MS according to USP chapters 232 and 233.

Along with the United States Pharmacopeia (USP) chapters 232 and 233 regarding elemental impurities in pharmaceutical products, new challenges have been imposed in terms of sample preparation procedures prior to inductively coupled plasma mass spectrometry analysis, considering the matrix complexities. As so, a new microextraction procedure assisted by ultrasound using a cup-horn sonoreactor, minimal reactants, and sample was proposed and validated according to USP. The procedure was optimized with samples of milled tablets and 3 different acid mixtures (HNO3, 3HNO3:1HCl, and 9HNO3:1HF) and it was compared with microwave-assisted acid digestion. In the validation step, recoveries ranging from 85 to 120 % and RSD below 10 % were obtained for 22 analytes (except Ag and Pt) with satisfactory linearity and good sensitivity. The method was then applied for 37 samples of antidepressants, which presented trace levels of As, Ba, Cd, Co, Cr, Cu, Ni, Pb, Pd, Sn, and V.

Pilot study: External surface contamination of gemcitabine and 5-fluorouracil on drug packaging.

INTRODUCTION: Antineoplastic drugs (ADs) are commonly used pharmaceuticals for anticancer treatments. It has previously been shown that the external surface of drug vials frequently is contaminated with ADs. More than a decade ago methods to prevent occupational exposure were introduced by using plastic coverage of the glass vials or packing vials in a secondary plastic container. The aim of the pilot study was to determine contamination levels of ADs on different parts of AD packaging of two different commercially available drug vials on the Swedish market and to investigate the occurrence of cross contamination of ADs. METHODS: Packagings of gemcitabine (GEM) and 5-fluorouracil (5-FU) were tested by wipe sampling. Five ADs; GEM, 5-FU, cyclophosphamide (CP), ifosfamide and etoposide were quantified using liquid chromatography mass spectrometry. RESULTS: AD contaminations were detected in 69% and 60% of the GEM and 5-FU packaging samples. Highest levels, up to approximately 5 µg/sample, were observed on the glass vials. The protective shrink-wrap of 5-FU vials and the plastic container of GEM were contaminated with low levels of 5-FU and GEM, respectively, and furthermore the 5-FU vials with shrink-wrap were cross-contaminated with GEM. Cross-contamination of CP and GEM was detected on 5-FU vials with plastic shrink-wrap removed. CONCLUSIONS: External contamination of ADs are still present at primary drug packagings on the Swedish market. Protection of AD vials by plastic shrink-wrap or a secondary plastic container does not remove the external contamination levels completely. The presence of cross contamination of ADs on drug packagings was also observed.

UHPLC-MS/MS Method Development and Validation for the Genotoxic Impurities Trimethyl Phosphate and Triisopropyl Phosphate of Elagolix Sodium.

Elagolix sodium is a gonadotropin-releasing hormone (GnRH) receptor antagonist that inhibits endogenous GnRH signaling by competitively binding to GnRH receptors in the pituitary gland to treat moderate to severe pain associated with endometriosis. To keep the safety and quality of the drug, a fast quantitative method by reversed-phase ultrahigh-performance liquid chromatography coupled with tandem mass spectrometry has been developed and validated for the identification, assay and estimation of potential genotoxic impurities trimethyl phosphate and triisopropyl phosphate in commercial batches of this active pharmaceutical ingredient in accordance with International Conference on Harmonization guidelines Q2 and M7. The method was validated by assessing specificity, sensitivity, linearity, the limit of quantification and detection, accuracy, precision and robustness for above analytes at a very low concentration, whose quantification and detection limits reached to 24 and 4.8 pg/ml, respectively, and the total run time for a single injection was 6 min.

Efficient extraction of adventitious virus nucleic acid using commercially available methods.

An essential step in pharmaceutical product development is screening for contamination with adventitious agents, and there is desire to develop highly sensitive assays to detect adventitious viral nucleic acid. This study sought to examine the nucleic acid extraction efficiency of three viral candidates in relevant background matrices using four different extraction methods. Three model adventitious viruses, Minute virus of Mice, Porcine Circovirus, and Feline Leukemia Virus, were diluted within a variety of background matrices relevant to pharmaceutical production methods. Upon extraction, the nucleic acid was quantified using droplet digital PCR methods. Four nucleic acid extraction methods were assessed, including commercially available kits and manual extraction methods. Each method recovered nucleic acid post-extraction for each of the model viruses within the tested background matrices. The silica-column based method recovered a greater amount of viral nucleic acid, compared to the other methods tested. Similar trends were observed when model virus was diluted in bioreactor supernatant, which replicates industry testing conditions and provides details on which extraction methods might be used in Next Generation Sequencing and PCR methods for detecting contamination within pharmaceutical products.

Fecal bacteria contamination in the Adriatic Sea: Investigating environmental factors and modeling to manage recreational coastal waters.

This study is based on assessing fecal indicator bacteria contamination along meteorological, hydrological and physical-chemical variables after high rainy events during the summer period. The study focused on four different coastal sites in the western and eastern Adriatic coast characterized by various geomorphological and hydrological features, levels of urbanization and anthropogenic pressures, with the aim of finding appropriate and effective solutions to ensure the safety and sustainability of tourism and public health. Detailed in-situ survey revealed a wide range of fecal indicator bacterial (FIB) across the different river mouths with concentrations of E. coli ranging from 165 to 6700 CFU 100 mL-1. It was found that nitrogen compounds track microbial load and acted as tracers for fecal contaminants. Further, a modelling tool was also used to analyze the spatial and temporal distribution of fecal pollution at these coastal sites. The integrated monitoring through high frequent survey in river waters and modeling framework allowed for the estimation of fecal indicator bacterial load at the river mouth and examination of fecal pollutant dispersion in recreational waters, considering different scenarios of fecal dispersion along the coast. This study formed the basis of a robust decision support system aimed at improving the management of recreational areas and ensuring the protection of water bodies through efficient management of bathing areas.

Arboviral Risk Associated with Solid Organ and Hematopoietic Stem Cell Grafts: The Prophylactic Answers Proposed by the French High Council of Public Health in a National Context.

Diseases caused by arboviruses are on the increase worldwide. In addition to arthropod bites, most arboviruses can be transmitted via accessory routes. Products of human origin (labile blood products, solid organs, hematopoietic stem cells, tissues) present a risk of contamination for the recipient if the donation is made when the donor is viremic. Mainland France and its overseas territories are exposed to a complex array of imported and endemic arboviruses, which differ according to their respective location. This narrative review describes the risks of acquiring certain arboviral diseases from human products, mainly solid organs and hematopoietic stem cells, in the French context. The main risks considered in this study are infections by West Nile virus, dengue virus, and tick-borne encephalitis virus. The ancillary risks represented by Usutu virus infection, chikungunya, and Zika are also addressed more briefly. For each disease, the guidelines issued by the French High Council of Public Health, which is responsible for mitigating the risks associated with products of human origin and for supporting public health policy decisions, are briefly outlined. This review highlights the need for a "One Health" approach and to standardize recommendations at the international level in areas with the same viral epidemiology.

No difference in bacterial contamination of hip capsule sutures and control sutures in hip arthroplasty surgery.

BACKGROUND: Perioperative preventive measures are important to further reduce the rate of periprosthetic joint infections (PJI) in patients undergoing total hip arthroplasty (THA). During THA surgery, joint capsule sutures are commonly placed to optimize exposure and reinsertion of the capsule. Bacterial contamination of these sutures during the procedure poses a potential risk for postoperative infection. In this exploratory study, we assessed the contamination rate of capsule sutures compared to the contamination of the remains of exchanged control sutures at the time of closure. METHODS: In 100 consecutive patients undergoing primary THA capsule sutures were exchanged by sterile sutures at the time of capsule closure. Both the original sutures and the remainder of the newly placed (control) sutures were retrieved, collected and cultured for ten days. Types of bacterial growth and contamination rates of both sutures were assessed. RESULTS: Sutures from 98 patients were successfully collected and analyzed. Bacterial growth was observed in 7/98 (7.1%) of the capsule sutures versus 6/98 (6.1%) of the control sutures, with a difference of 1% [CI -6-8]. There was no clear pattern in differences in subtypes of bacteria between groups. CONCLUSIONS: This study showed that around 7% of capsule sutures used in primary THA were contaminated with bacteria and as such exchange by new sutures at the time of capsule closure could be an appealing PJI preventive measure. However, since similar contamination rates were encountered with mainly non-virulent bacteria for both suture groups, the PJI preventive effect of this measure appears to be minimal.

Identification of low-level impurities in drug prototypes of carbocisteine by means of liquid chromatography-high-resolution mass spectrometry and general unknown comparative screening.

High-resolution tandem quadrupole time-of-flight mass analysers enable new automated workflows for untargeted data evaluation of complex samples like drug products. An example of such procedure is the so-called general unknown comparative screening (GUCS), which is used for software-assisted, automated identification of components that are only present in a sample and not in a reference. The GUCS approach has been employed for the first time to detect both degradation products and reaction products in drug products. Two different carbocisteine containing syrup prototypes - one with sucrose and the other with artificial sweeteners - were selected as examples after nine months of storage at 40 °C and 75% relative humidity. The samples were analysed chromatographically using a Coresep SB mixed-mode column and high-resolution MS and MS/MS data were recorded in information dependant acquisition mode on a Sciex X500R quadrupole time-of-flight mass spectrometer. Data analysis was considerably facilitated using the corresponding placebo formulation as reference samples. With the GUCS approach two hitherto unknown degradation products of carbocisteine, i.e. the carbocisteine lactam of the sulfoxides and the disulfide between l-cysteine and thioglycolic acid, were detected at low concentrations in both of the syrup formulations. The presumed structures were confirmed by in silico analysis of the fragment spectra and high-resolution LC-MS experiments with reference substances. Two additional impurities were found in the sucrose-containing sample and identified as the N-glycosides of carbocisteine and its lactam, respectively, using binary mixtures with a 13C-labelled monosaccharide.

An update on formaldehyde adulteration in food: sources, detection, mechanisms, and risk assessment.

Formaldehyde is added illegally to food to extend its shelf life due to its antiseptic and preservation properties. Several research has been conducted to examine the consequences of adulteration with formaldehyde in food items. These findings suggest that adding formaldehyde to food is considered harmful as it accumulates in the body with long-term consumption. In this review includes study findings on food adulteration with formaldehyde and their assessment of food safety based on the analytical method applied to various geographical regions, food matrix types, and their sources in food items. Additionally, this review sought to assess the risk of formaldehyde-tainted food and the understanding of its development in food and its impacts on food safety in light of the widespread formaldehyde adulteration. Finally, the study would be useful as a manual for implementing adequate and successful risk assessment to increase food safety.

Maximizing use of existing carcinogenicity data to support acceptable intake levels for mutagenic impurities in pharmaceuticals: Learnings from N-nitrosamine case studies.

The unexpected finding of N-nitrosamine (NA) impurities in many pharmaceutical products raised significant challenges for industry and regulators. In addition to well-studied small molecular weight NAs, many of which are potent rodent carcinogens, novel NAs associated with active pharmaceutical ingredients have been found, many of which have limited or no safety data. A tiered approach to establishing Acceptable Intake (AI) limits for NA impurities has been established using chemical-specific data, read-across, or a class-specific TTC limit. There are ∼140 NAs with some rodent carcinogenicity data, but much of it is older and does not meet current guidelines for what constitutes a 'robust' bioassay. Nevertheless, these data are an important source of information to ensure the best science is used for assessing NA impurities and assuring consumer safety while minimizing impact that can lead to drug shortages. We present several strategies to maximize the use of imperfect data including using a lower confidence limit on a rodent TD50, and leveraging data from multiple NAs. Information on the chemical structure known to impact potency can also support development of an AI or potentially conclude that a particular NA does not fall in the cohort of concern for potent carcinogenicity.

Immunogenicity risk assessment of synthetic peptide drugs and their impurities.

Peptide drugs play an important part in medicine owing to their many therapeutic applications. Of the 80 peptide drugs approved for use in humans, at least five are now off-patent and are consequently being developed as generic alternatives to the originator products. To accelerate access to generic products, the FDA has proposed new regulatory pathways that do not require direct comparisons of generics to originators in clinical trials. The 'Abbreviated New Drug Application' (ANDA) pathway recommends that sponsors provide information on any new impurities in the generic drug, compared with the originator product, because the impurities can have potential to elicit unwanted immune responses owing to the introduction of T-cell epitopes. This review describes how peptide drug impurities can elicit unexpected immunogenicity and describes a framework for performing immunogenicity risk assessment of all types of bioactive peptide products. Although this report primarily focuses on generic peptides and their impurities, the approach might also be of interest for developers of novel peptide drugs who are preparing their products for an initial regulatory review.

On the Risk of Nitrosamine Contamination During Drug Product Blister Packaging.

Most N-Nitrosamine compounds are found to be genotoxic in several animal species. Some are classified as probable or possible human carcinogens and very low acceptable daily intake has been established such as 96 ng/day for N-nitrosodimethylamine (NDMA) and 26.5 ng/N-nitrosodiethylamine (NDEA). The pharmaceutical industry has considered all processing areas for potential formation or contamination of N-nitrosamine. One risk is the potential contamination of nitrosamine during drug product blister packaging using lidding foils containing nitrocellulose, and different approaches have been used by pharmaceutical companies to evaluate and mitigate this risk. Herein we share a perspective from IQ Consortium N-nitrosamine Working Group on some of the approaches and corresponding results. From these assessments, it was concluded that the risk of nitrosamine contamination during blister packaging is negligible. The approaches shared in this perspective can be incorporated into risk assessment for nitrosamine contamination during drug product packaging at other pharmaceutical companies.

[Design and application of a new transoral gastric tube for extraction and storage of gastric contents].

Difficulty in swallowing is a common symptom in stroke patients, and nasogastric tubes are routinely used to solve the nutritional support problem of these patients. The existing nasogastric tube have the disadvantages of causing aspiration pneumonia and patient discomfort. The traditional transoral gastric tube has no one-way valve switch and gastric content storage device, and cannot be fixed in the stomach, resulting in reflux of gastric contents, inability to fully understand the digestion and absorption of gastric contents, and accidental dislocation of the gastric tube, affecting further feeding and gastric content detection. For these reasons, the medical staff of the department of gastroenterology and colorectal surgery of Jilin University China-Japan Union Hospital designed a new transoral gastric tube that can extract and store gastric contents, and was granted a national utility model patent of China (ZL 2020 2 1704393.1). The device consists of collection, cannula and fixation modules. The collection module includes three parts. Gastric contents storage capsule, which can clearly visualize the gastric contents; three-way switch, which can be controlled by rotating the pathway, makes the pathway exist in different states, which is convenient for medical personnel to extract gastric juice, as well as perform intermittent oral tube feeding on the patient or close the pipeline, and reduce contamination and prolong the service life of the gastric tube; one-way valve, which can effectively avoid the contents of the reflux back into the stomach. The tube insertion module includes three parts. A graduated tube, which can enable the medical staff to effectively identify the insertion depth; a solid guide head, which makes the insertion of the tube through the mouth more smoothly; the gourd-shaped passageway, which effectively avoids the blockage of the tube. The fixation module is a water-filled balloon, which is properly filled with water and air. After the pipe is inserted through the mouth, it can be injected with water and gas properly to avoid accidental withdrawal of the gastric tube. Intermittent oroesophageal tube feeding of patients with dysphagia after stroke through a transoral gastric tube that can extract and store gastric contents can not only accelerate the recovery process of patients and shorten the hospitalization time, but also transoral enteral nutrition can effectively promote the recovery of patients' systemic systems, which has certain clinical use value.