Residual Organic Solvents Research Articles

Gravimetric and SIM-Headspace GC-MS for Residual Organic Solvents Detection in Halal and Wholesomeness Food Analysis

The demand for halal foods and beverages is increasing globally. While most halal analysis focuses on porcine, this study focuses on assessing residual organic solvents to ensure their halal compliance and wholesomeness, following several Malaysian standards and guidelines. A significant challenge in this study was the volatility of the residual solvents during the preparation of standards and quality control. To address this issue, a gravimetric technique was employed and effectively minimized the difference between theoretical (1,000 ppm) and actual (710 – 892 ppm) concentrations of the residual organic standard stock solution, except for acetone (588 ppm). The aim of this study was to establish a validated, reliable, and accurate method using SIM-headspace GC-MS to identify and quantify residual organic solvents for halal and wholesomeness analysis. Confirmation of each residual organic solvent was achieved by comparing the obtained spectra with the NIST 11 spectral database, containing 70,832 compounds, with similarity ranging from 80.9% to 96.6%, except for acetonitrile at 52.2%. The validation parameters were carried out according to ISO 17025:2017, the Center for Drug Evaluation and Research, and the European Guidelines. The parameters included recovery ranging from 95.65% to 95.68%, precision from 10.08% to 19.65% RSD, linearity between 0.996 to 0.999, limit of detection from 0.01 to 0.08 ppm, and limit of quantification from 0.02 to 0.24 ppm. Uncertainty considerations were limited to recovery, precision, and linearity, as other uncertainties were negligible based on the bottom-up approach using in-house validation data. This combination of gravimetric and SIM-headspace GC-MS techniques has provided valuable insights for discussions and collaborations among halal authorities worldwide to establish a consensus analytical methodology for halal and wholesomeness assessment.

Accelerated removal of solvent residuals from PLGA microparticles by alcohol vapor-assisted fluidized bed drying

The removal of residual solvents from biodegradable poly(D,L-lactide-co-glycolide) (PLGA) microparticles by fluidized bed drying was investigated. Microparticles were prepared by the O/W solvent extraction/evaporation method and the influence of various process and formulation parameters on the secondary drying was studied. PLGA microparticles and films were characterized for residual organic solvent and water content, recrystallisation, surface morphology, drug loading and in-vitro release of the drugs dexamethasone and risperidone. While alcohol-free fluidized bed drying decreased the residual dichloromethane content only from about 7 % (w/w) to 6.4 % (w/w) (18 °C) or 3.2 % (w/w) (35 °C) within 24 h, 140 mg/L methanol vapor in purge gas facilitated almost complete removal of dichloromethane or ethyl acetate from microparticles (0–0.11 % (w/w) after 6 h). By controlling the alcohol concentration and temperature of the purge gas, the alcohol absorption and complete removal was controlled. Risperidone increased the methanol absorption enhancing the plasticization. A high initial residual water content was identified to promote aggregation and was eliminated by starting fluidized bed drying without alcohol. Alcohol vapor-assisted fluidized bed drying accelerated microparticle manufacturing without affecting the redispersibility, the drug loading and the in-vitro release of risperidone and dexamethasone.

Production of liposomes by microfluidics: The impact of post-manufacturing dilution on drug encapsulation and lipid loss

Microfluidic mixing is recognized as a convenient method to produce liposomes for its scalability and reproducibility. Numerous studies have described the effect of process parameters such as flow rate ratios and total flow rate on size and size distribution of vesicles. In this work, we focused our attention on the effect of flow rate ratios on the encapsulation efficiency of liposomes, as we hypothesized that different amount of residual organic solvent could affect the retention of lipophilic drug molecules within the bilayer. In a further step, we investigated how the liposomes integrity and loading were impacted by different methods of solvent removal: direct dialysis and dilution & dialysis. Liposomes were prepared by rapidly mixing an ethanolic solution of lipids and a model drug with buffer in a herringbone micromixer, employing four different flow rate ratios (FRR, 4:1, 7:3, 3:2, 1:1). Quercetin, resveratrol and ascorbyl palmitate were used as model antioxidant drugs with different lipophilicity. Data showed that liposomes produced using lower flow rate ratios (i.e., with more residual ethanol) had lower encapsulation efficiencies as well as a more prominent loss of lipids from the bilayer following purification with direct dialysis. If the amount of residual ethanol was reduced to 5% (dilution & dialysis method), the lipids and drug leakage was prevented. Such effect was correlated with the drug aggregation propensity in different ethanol/water mixtures measured by molecular dynamics simulations. Overall, these results highlight the need to tailor the purification method basing on the molecular properties of the loaded drug to ensure high encapsulation and limit the waste of material.

Enhancing the Nutritional Quality of Defatted Cottonseed Meal by Solid-State Fermentation with Probiotic Microbes

Defatted cottonseed meal (DCSM), a byproduct of the cotton industry, is highly regarded for its high protein content, making it a source of nutrients in animal feed. Traditional physical and chemical treatments of DCSM can lead to a reduction in nutrient content and the presence of residual organic solvents. Probiotic fermentation of DCSM offers several advantages, including degradation of anti-nutritional factors, an increase in nutrient content, and production of beneficial metabolites. This study employed probiotic fermentation of DCSM using a probiotic microbe collection composed of Saccharomyces cerevisiae, Enterococcus faecium, and Lactiplantibacillus plantarum. This fermentation process significantly enhanced the nutritional quality of DCSM. Specifically, the contents of crude protein, free amino acid, total phosphorus, and moisture increased by 1.14-fold, 1.14-fold, 1.24-fold, and 3-fold, respectively. In the meanwhile, there was a substantial reduction in the content of dry matter, crude ash, and crude fat, with decreases of 27.83%, 25.74%, and 88.23%, respectively. Probiotic fermentation of DCSM resulted in an overall enhancement of the palatability of DCSM. This study provides valuable insights into the potential of mixed probiotic fermentation as a promising approach for improving the nutritional quality of DCSM.

Toward a large-batch manufacturing process for silicon-stabilized lipid nanoparticles: A highly customizable RNA delivery platform

While lipid nanoparticles (LNPs) are a key enabling technology for RNA-based therapeutics, some outstanding challenges hinder their wider clinical translation and use, particularly in terms of RNA stability and limited shelf life. In response to these limitations, we developed silicon-stabilized hybrid lipid nanoparticles (sshLNPs) as a next-generation nanocarrier with improved physical and temperature stability, as well as the highly advantageous capacity for “post-hoc loading” of RNA. Nevertheless, previously reported sshLNP formulations were produced using lipid thin film hydration, making scale-up impractical. To realize the potential of this emerging delivery platform, a manufacturing process enabling multikilogram batch sizes was required for successful clinical translation and deployment at scale. This was achieved by developing a revised protocol based on solvent injection mixing and incorporating other process adjustments to enable in-flow extrusion of multiliter volumes, while ensuring sshLNPs with the desired characteristics. Optimized procedures for nanoparticle formation, extrusion, and tangential flow filtration (TFF, to remove residual organic solvent) currently enable production of 2 kg finished batches. Importantly, sshLNPs produced via the modified large-scale workflow show equivalent physical and functional properties to those derived from the earlier small-scale methods, paving the way for GMP manufacturing protocols to enable vital translational clinical studies.

Purity Assessment of Tripropyl Phosphate through Mass Balance and 1H and 31P Quantitative Nuclear Magnetic Resonance.

Tripropyl phosphate (TnPP) is a commonly used organic phosphate flame retardant in the textiles, plastics, and coating industries. Residues are commonly detected in samples from the environment and food. The availability of certified reference materials (CRMs) is essential to ensure the accuracy and traceability of detection results. In this study, a comprehensive characterization of a CRM for TnPP was carried out, and its purity was evaluated using two distinct methodologies: mass balance (MB) and quantitative nuclear magnetic resonance spectroscopy (qNMR). In the MB method, the levels of structurally related organic impurities are 1.37 mg/g. The water content was determined to be 3.16 mg/g, while inorganic impurities were found to be 0.87 mg/g, and no residual organic solvents were detected. Benzoic acid and monocrotophos were chosen as internal standards for 1H-qNMR and 31P-qNMR, respectively. The purity of the TnPP CRM was assessed as 994.6 mg/g, 994.1 mg/g, and 993.5 mg/g using MB, 1H-qNMR, and 31P-qNMR techniques, respectively. The verified purity of the TnPP CRM was ultimately determined to be 994.1 mg/g, with an expanded uncertainty of 3.4 mg/g (k = 2), ensuring traceability to the International System of Units (SI). This CRM can be effectively utilized for preparing calibration solutions suitable for the routine monitoring of TnPP residues in plastics and food samples.

Efficient E/Z conversion of (all-E)-lycopene to Z-isomers with a high proportion of (5Z)-lycopene by food grade plant extracts

The conversion of lycopene from natural sources, mainly in all trans configurations, to cis configuration means a significant increase in bioavailability. However, the existing isomerization methods have problems with residual organic solvents, which limits the use of products. such as metal ion catalysis, electrocatalysis, and iodine-doped titanium dioxide (I–TiO2) catalysis. In this paper, the effects of common plant extracts on lycopene isomerization and its stability were investigated. Among them, sulforaphane and allicin showed significant catalytic effects, with sulforaphane being the most effective. Therefore, Broccoli sprouts were selected as a food component to investigate the catalytic isomerization of lycopene. After the optimization of pretreatment, the final content of sulforaphane was 5.81 mg/g. The cis-proportion of lycopene was elevated from 5% in the blank group to more than 60% when the treated broccoli sprout paste was added to the tomato paste. Also, the bioavailability of lycopene increased significantly with the increase in cis proportion. Compared with other isomerization methods, the method studied in this paper does not require any organic reagents and only uses food-grade materials such as allicin, sulforaphane, and broccoli sprouts to catalyze the cis-trans isomerization of lycopene.

Effect of PLGA raw materials on in vitro and in vivo performance of drug-loaded microspheres.

Poly(lactide-co-glycolide) and poly(lactic-co-glycolic acids) (PLGAs) play a critical role in the development of commercial long-acting injectable microsphere formulations. However, very little information is available describing the impact of PLGA manufacturer and monomer distribution along the polymer chain (e.g., glycolic blockiness (Rc) and average lactic block length (LL)) on the degradation and release behavior of PLGA drug carriers in vitro and in vivo. Here, we compared the in vitro and in vivo performance of (a) four leuprolide-loaded microsphere formulations prepared from similar low-molecular-weight acid-capped PLGAs (10-14 kD, i.e., Expansorb® DLG 75-2A, Purasorb® PDLG 7502A, Resomer® RG 752H and Wako® 7515) and (b) two triamcinolone acetonide-loaded (Tr-A) microsphere formulations from similar medium-molecular-weight ester-capped PLGAs (i.e., Expansorb® DLG 75-4E and Resomer® RG 753S). Lupron Depot® and Zilretta® were used as reference commercial products. The six 75/25 PLGAs displayed block lengths that were either above or below values expected from a random copolymer. Drug release and polymer degradation were monitored simultaneously in vitro and in vivo using a cage implant system. The four leuprolide-loaded formulations showed similar release and degradation patterns with some notable differences between each other. Microspheres from the Expansorb® polymer displayed lower LL and higher Rc relative to the other 3 PLGA 75/25 microspheres, and likewise exhibited distinct peptide release and degradation behavior compared to the other 3 formulations. For each formulation, leuprolide release was erosion-controlled up to about 30% release after the initial burst followed by a faster than erosion release phase. In vitro release was similar as that in vivo over the first phase but notably different from the latter release phase, particularly for the most blocky Expansorb® formulation. The Purasorb® and Wako® formulations displayed highly similar performance in release, degradation, and erosion analysis. By contrast, the two ester-capped Expansorb® DLG 75-4E and Resomer® RG 753S used to prepare Tr-A microspheres shared essentially identical LL and higher Rc and behaved similarly although the Expansorb® degraded and released the steroid faster in vivo, suggestive of other factors responsible (e.g., residual monomer). The in vivo release performance for both drugs from the six microsphere formulations was similar to that of the commercial reference products. In summary, this work details information on comparing the similarities and differences in in vitro and in vivo performance of drug-loaded microspheres as a function of manufacturing and microstructural variables of different types of PLGA raw materials utilized and could, therefore, be meaningful in guiding the source control during development and manufacturing of PLGA microsphere-based drug products. Future work will expand the analysis to include a broader range of LL and higher Rc, and add additional important formulation metrics (e.g., thermal analysis, and residual monomer, moisture, and organic solvent levels).

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.

Pitfalls in RNA Modification Quantification Using Nucleoside Mass Spectrometry.

In recent years, there has been a high interest in researching RNA modifications, as they are involved in many cellular processes and in human diseases. A substantial set of enzymes within the cell, called RNA writers, place RNA modifications selectively and site-specifically. Another set of enzymes, called readers, recognize these modifications which guide the fate of the modified RNA. Although RNA is a transient molecule and RNA modification could be removed by RNA degradation, a subclass of enzymes, called RNA erasers, remove RNA modifications selectively and site-specifically to alter the characteristics of the RNA. The detection of RNA modifications can be done by various methods including second and next generation sequencing but also mass spectrometry. An approach capable of both qualitative and quantitative RNA modification analysis is liquid chromatography coupled to mass spectrometry of enzymatic hydrolysates of RNA into nucleosides. However, for successful detection and quantification, various factors must be considered to avoid biased identification and inaccurate quantification. In this Account, we identify three classes of errors that may distort the analysis. These classes comprise (I) errors related to chemical instabilities, (II) errors revolving around enzymatic hydrolysis to nucleosides, and (III) errors arising from issues with chromatographic separation and/or subsequent mass spectrometric analysis.A prominent example for class 1 is Dimroth rearrangement of m1A to m6A, but class 1 also comprises hydrolytic reactions and reactions with buffer components. Here, we also present the conversion of m3C to m3U under mild alkaline conditions and propose a practical solution to overcome these instabilities. Class 2 errors-such as contaminations in hydrolysis reagents or nuclease specificities-have led to erroneous discoveries of nucleosides in the past and possess the potential for misquantification of nucleosides. Impurities in the samples may also lead to class 3 errors: For instance, issues with chromatographic separation may arise from residual organic solvents, and salt adducts may hamper mass spectrometric quantification. This Account aims to highlight various errors connected to mass spectrometry analysis of nucleosides and presents solutions for how to overcome or circumnavigate those issues. Therefore, the authors anticipate that many scientists, but especially those who plan on doing nucleoside mass spectrometry, will benefit from the collection of data presented in this Account as a raised awareness, toward the variety of potential pitfalls, may further enhance the quality of data.

TECHNOLOGY OF OBTAINING THE SUM OF IRIDOIDS FROM THE WASTE PROCESSING THE AERIAL PART OF AJUGA TURKESTANICA

The processes studied of sedimentation and purification of the number of iridoids from the processing waste of the aerial part of Ajuga turkestanica Regel. Brig. (Turkestan tenacious). Based on the results of the research, it was found that for the effective precipitation of iridoids, the ethanol extract from the aerial part of the Turkestan tenacious is concentrated, diluted with water, treated successively with extraction gasoline and ethyl acetate, from the purified solution iridoids and ecdysteroids, are extracted with n-butanol, then the n-butanol extract is concentrated to 1/10 of the initial volume, after which the iridoids are precipitated, by pouring acetone in a volume ratio of n-butanol-acetone 1 : 5, the precipitate is separated and dried. To clean accompanying substances, the dried amount of iridoids is dissolved in ethyl alcohol and re-precipitated by pouring ethyl acetate in a volume ratio of ethyl alcohol-ethyl acetate 1 : 5. Experiments were carried out on the selection of the type of drying apparatus and the establishment of optimal drying conditions. It was revealed that drying the sum of iridoids from the aerial part of the Turkestan tenacious in the "ZPG 150" spray dryer is more optimal than drying in a drying cupboard (vacuum and without vacuum) and an infrared drying cupboard. At the same time, for drying in the "ZPG 150" spray dryer, the dried aqueous solution of iridoids must be prepared as follows: after the second precipitation, the sum of iridoids is dissolved with water until about 7% of the dry residue in the solution is formed and, with the aim of removing residual organic solvents, the aqueous solution of iridoids is concentrated to the content of not more than 15% and not less than 10% of the dry residue. It has been established that to obtain a finished product that is stable in yield and quality, drying an aqueous solution of iridoids in a spray dryer "ZPG 150" must be carried out implemented at a temperature coolant at the inlet 170 °С, at an outlet of 80 °C and a solution feed rate of 80 l/h, spray head rotation speed 8000 rpm and coolant speed 2200 kg/h. Technology has been developed for the production of the substance of iridoids from the waste products of the production of ekdisten from the aerial part of Turkestan tenacious, which allows the rational use of plant raw materials. Approbation of the developed technology showed that the yield of the target product is 1.5% by weight of the raw material.

Pollen allergen products: current standardisation issues

Scientific relevance. Pollen allergen medicines are in high demand, and their therapeutic benefits directly correlate with their standardisation. Better diagnosis and treatment of allergic diseases require state-of-the-art procedures for assessing the allergenic activity of pollen allergen products using reference standards and physicochemical testing methods.Aim. The study aimed at developing methodological approaches to the standardisation of pollen allergen products in order to shift to measuring their potency in allergenic activity units (AAU) and bring their quality in line with the requirements of the State Pharmacopoeia of the Russian Federation.Materials and methods. The study used pollen allergen reference standards by Microgen, the WHO International Standard for timothy grass (Phleum pratense) pollen extract, a gel filtration standard kit of molecular weight markers ranging from 1.35 to 670 kDa, bovine serum albumin, serum samples with specific IgE obtained from donors sensitised to the study pollen allergens, labelled anti-human IgE antibodies, and reference standards for determining residual volatile solvents by gas chromatography. The identification of in-house reference standards for the potency of pollen allergens involved Western blotting (for allergenic components). The total protein content was determined by Bradford’s assay. In addition, the authors used high-performance liquid chromatography to study protein fractions and gas–liquid chromatography to determine the content of residual organic solvents.Results. To substitute the existing method of non-specific characterisation of allergenic activity in protein nitrogen units (PNU), the authors developed and tested a new method to control allergenic activity in allergenic activity units (AAU) based on an in vitro competitive enzyme-linked immunosorbent assay (ELISA) procedure developed and validated in this study. Furthermore, the authors developed and certified 15 primary in-house reference standards with allergenic activity established in AAU/mL using skin tests in vivo. The experimental data were analysed to standardise the allergenic activity of the pollen allergens manufactured by Microgen. The authors developed physicochemical methods for the certification of in-house reference standards and validated these methods in accordance with the State Pharmacopoeia of the Russian Federation. The study involved selecting chromatographic separation conditions for residual organic solvents (acetone and diethyl ether) and establishing system suitability criteria for the chromatographic system. The allergenic activity of secondary in-house reference standards was certified against that of primary in-house reference standards using competitive ELISA. Thus, the authors managed to shift to the standardisation of pollen allergen products in vitro.Conclusions. The authors developed their competitive ELISA-based method to standardise pollen allergen products by comparing the inhibition of immune responses to a product and a standard. The study demonstrated the feasibility of substituting allergenic activity quantification (in AAU) for protein nitrogen content determination (in PNU) and showed the first example of using AAU for the certification of in-house reference standards. Additionally, the authors developed and validated an analytical procedure for determining the content of residual organic solvents in pollen allergen products by gas–liquid chromatography.

Synthesis of highly stable encapsulated astaxanthin/β-cyclodextrin microparticles using supercritical CO2 as an antisolvent

Although astaxanthin has promising physiological functions, its practical applications are limited by poor stability. Herein, astaxanthin was encapsulated in β-cyclodextrin (βCD) using CO2 as a supercritical antisolvent (SAS). The effects of process conditions, including temperature (313–333 K), pressure (12–18 MPa), solution concentration (3–5 wt%), solution flow rate (0.8–1.2 mL min−1), and astaxanthin-to-βCD mole ratio (1:50, 1:25, or 1:10), on the encapsulation efficiency, particle morphology, and residual solvent content were investigated. Astaxanthin–βCD complex spheres with an average diameter of 0.44 ± 0.08 µm were produced at 313 K and 15 MPa with a solution concentration and flow rate of 5 wt%, and 1.0 mL min−1, respectively. Under these optimal conditions, almost complete encapsulation (99.6% encapsulation efficiency) and residual organic solvent removal (0.22 ppm in the complex) were achieved. Density functional theory analysis of the configuration of the astaxanthin–βCD complex indicate that the hydroxyl hydrogen atoms on an ionone ring of astaxanthin interact with the oxygen atoms of βCD, but the ionone ring does not fit deeply within the βCD cavity. Notably, the astaxanthin–βCD complex exhibits higher thermal stability and antioxidant activity than free astaxanthin. The findings suggest that βCD encapsulation via the SAS process can produce astaxanthin microparticles with potential utility for food and pharmaceutical applications.

Standardization of the Pharmaceutical Substance of Lithium Salt Gamma-lactone of 2,3-dehydro-l-gulonic Acid as a Radio-sensitizing Agent

Introduction. It was found that in combination with radiation exposure, high doses of lithium salts have a depressing effect on tumor leukemia cells. The selection of the appropriate anionic component makes it possible to obtain pronounced radiosensitizing properties. The lithium salt of gamma-lactone 2,3-dehydro-L-gulonic acid is a promising compound for the creation of radiosensitizing drugs. It was found that this compound exhibits high antioxidant activity among other lithium salts, while showing a pronounced radiosensitizing effect. This radiosensitizing effect is dose-dependent and manifests itself in high concentrations in combination with photon or neutron irradiation. The potential antitumor effect, due to radiosensitization, is realized through the induction of oxidative stress, which implies, first of all, an increase in cytotoxic effects on rapidly proliferating tumor cells. The obtained results provide the necessary basis for the creation of drugs with radiosensitizing activity.Aim. The aim of this work is to conduct an analytical assessment of the content of the active substance and establish the main indicators of the quality of the substance, regulated by the State Pharmacopoeia of the Russian Federation.Materials and methods. During the study, the following parameters were determined: solubility, authenticity, melting point, refractive index, specific rotation, transparency of the solution, color of the solution, pH of the solution, sulfate ash, heavy metals, impurities, water content, residual organic solvents, microbiological purity and a number of others.Results and discussion. A draft specification for the pharmaceutical substance of the lithium salt gamma-lactone 2,3-dehydro-L-gulonic acid has been developed. The optimal parameters for the control of the composition and physico-chemical characteristics and quantitative determination of the pharmaceutical substance have been determined, which is the main task for the pharmaceutical development of the drug. The results obtained make it possible to conduct a comprehensive characterization of the FS and evaluate the quality parameters of the product, which creates the basis for obtaining a dosage form and further studying the properties for creating a drug with a radiosensitizing effect.Conclusion. In the course of the work, experimental samples of the lithium salt gamma-lactone 2,3-dehydro-L-gulonic acid were synthesized and its standardization as a pharmaceutical substance was carried out in accordance with the requirements of the State Pharmacopoeia of the Russian Federation.

Laser waterless cleaning of residual organic solvents on the surface of polyurethane coatings.

Residual organic solvents have a great impact on the physical and mental health of equipment operators in industry and agriculture. Laser waterless cleaning technology of residual organic solvents on the surface of polyurethane coatings has great application prospects and is a good way to tackle the pollution problem. In this paper, the evolutionary behavior of a laser waterless cleaning mechanism and substrate surface state is analyzed. The influence law of laser energy density and scanning speed on the residual solvent cleaning effect was investigated. The optimal laser cleaning parameters were obtained by comprehensive evaluation of the substrate surface cleaning effect and microscopic morphology. The peak of solvent characteristics before and after laser cleaning was detected by Raman spectroscopy. The results demonstrated that the laser cleaning effect was better with the increase of energy density or the decrease of scanning speed in the substrate damage range, and the best laser cleaning parameters were laser energy density of 0.24J/c m 2 and scanning speed of 500mm/s. A significant reduction of the peak of Raman spectroscopy was found, reflecting the excellent effect of laser waterless cleaning of residual organic solvents.

Experimentation and optimization of laser waterless decontamination rate of residual organic solvents

Laser waterless decontamination is a widely researched area for the high pollution issue of residual organic solvents in industry and agriculture. In this research, a nanosecond pulsed laser was used to conduct waterless decontamination studies on organic solvent residues on the surface of optical glass. A single-factor test was designed using the decontamination rate (Y) as the response value and the laser power (X1), scanning speed (X2), and decontamination times (X3) as the influencing variables. The Raman spectrum reflected the decontamination effect of organic solvent decontamination using a waterless laser. The Box-Behnken response surface method (RSM) was used to design the experiments. The developed RSM was used to determine the link between laser parameters and decontamination rate, and optimum decontamination parameters were determined. In addition, the mathematical model and regression equation were established using Design-Expert. The findings demonstrate that residual solvent may be removed at a rate of up to 95.22%. Optimum values for laser power, scanning speed, and decontamination times are 130 W, 381 mm/s, and 10 times respectively.

Extraction of Novel Bioactive Peptides from Fish Protein Hydrolysates by Enzymatic Reactions

Bioactive peptides derived from fish the byproduct protein hydrolysate have wide potential as functional food ingredients. The preparation of bioactive peptides is commonly achieved via enzymatic hydrolysis; this is the most preferred method because it has high specificity, fewer residual organic solvents in the product, and it is usually carried out in mild conditions. The use of various enzymes such as proteases is widely practiced in the industry, yet there are various limitations as it is of high cost and there is a limited availability of food-grade enzymes in the market. Moreover, high-throughput purification and the identification analysis of these peptides are currently being studied to further understand the functionality and characterization of the bioactive peptides. This review mainly focuses on the novel bioactive peptides derived from fish protein hydrolysates from various fish wastes and byproducts. The hydrolysis conditions, source of hydrolysate, and amino acid sequence of these novel peptides are presented, along with their corresponding methods of analysis in purification and identification. The use of various enzymes yields novel peptides with potent bioactivities, such as antiproliferative, antimicrobial, antihypertensive, antiglycemic, antitumor, and antioxidative biological functions. The increasing interest in proteomics in marine and aquatic waste utilization continues due to these products’ bioactivity and sustainability.

Abstract 3378: Rapid and efficient sample preparations for cell free DNA

Abstract The analysis of cell-free DNA (cfDNA) as a sensitive biomarker for cancer prognosis, diagnosis and monitoring resulted in a need for efficient and fast cfDNA isolation. The traditional cfDNA purification methods using chaotropic solvent to separate nucleic acids from plasma through column or magnetic bead purification processes are usually laborious and time consuming, involving multiple washing steps, and the residual organic solvent could be carried over to the elution solution that could cause downstream PCR inhibition. Herein, we developed a novel particle surface chemistry that can biochemically bind rapidly (<1min) and release nucleic acids rapidly (<1min) under different buffer conditions without needing chaotropic solvent. We further optimized the binding and elution buffer solutions that allow to isolate cfDNA from plasma within 5-10 minutes in the sample volumes from 1 ml to 4 ml. The real-time quantitative PCR indicated DNA extraction yields were comparable or slightly better than the traditional methods for both small and large volumes. The novel bead chemistry and the optimized binding and elution buffers are not only compatible to high throughput format but could also be applied to a variety sample types for rapid sample preparations. Citation Format: Zhiyang Zeng, Andrew Taft, Kasen Riemersma, Connor Fitzgerald, Mike Scurria, Spenccer Hermanson, Wenhui Zhou. Rapid and efficient sample preparations for cell free DNA [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3378.

Nanofibres in Drug Delivery Applications

Over the years, scientists have been continually striving to develop innovative solutions to design and fabricate medicines with improved therapeutic potential. Conventional dosage forms, such as tablets, capsules, and injections, are limited when exploited for advanced therapeutics, such as drug targeting. To cater to these limitations, nanofibres have emerged as novel nanomaterials to provide enhanced bioavailability, targeted drug release, extended drug release profile, minimum toxicity, and reduced dosage frequency, which has indisputably improved patient adherence and compliance. This review will concern understanding the potential of drug-loaded nanofibres in drug delivery while comprehending a detailed description of their different production methods. The literature has been thoroughly reviewed to appreciate their potential in developing nanofibrous-based pharmaceutical formulations. Overall, this review has highlighted the importance, versatility, and adaptability of nanofibres in developing medicines with varied drug release kinetics. Several problems must be resolved for their full commercial realisation, such as the drug loading, the initial burst effect, the residual organic solvent, the stability of active agents, and the combined usage of new or existing biocompatible polymers.

Anionic liposomes prepared without organic solvents for effective siRNA delivery.

Currently, organic solvents are necessary for the preparation of anionic liposomes for siRNA delivery. The removal of organic solvent is time-consuming and the residual organic solvent is not only a hidden danger, but also affects the stability of anionic liposomes. Glycerol, which is physiologically compatible and does not need to be removed, is used to promote the dispersion of lipids and the formation of anionic liposomes. Additionally, the preparation process is simple and not time-consuming. The results showed that anionic liposomes, which were typically spherical with a particle size of 188.9nm were successfully prepared with glycerol. And with the help of Ca2+ , siRNA was encapsulated in anionic liposomes. The highest encapsulation efficiency at 2.4mM Ca2+ reached 91%. And the formation of calcium phosphate could promote the endosomal escape of siRNA effectively. The results from cell viability showed that the anionic liposomes had no obvious cytotoxicity. It was also verified that anionic liposomes could improve the resistance of siRNA against degradation. Additionally, siRNA delivered by anionic liposomes could play an effective role in knockout. Therefore, anionic liposomes prepared with glycerol will be a safe and effective delivery platform for siRNA and even other nucleic acid drugs.