Химико-фармацевтический журнал

Bistorta amplexicaulis (D.Don) Greene from the family Polygonaceae is an important medicinal plant species. The growing therapeutic use of B. amplexicaulis has led to its population depletion thus requiring its conservation. Herein, an efficient, reproducible and reliable propagation protocol system was established for B. amplexicaulis using nodal segments as explant. Various culture media were tested for the assessment of growth and development of this plant species. On the shoot proliferation and rhizogenesis of regenerated B. amplexicaulis plantlets, the effects of several plant growth regulators (PGRs) were assessed. Direct organogenesis from nodal segments was achieved by culturing the nodal explants on Murashige and Skoog medium supplemented with 2.0 mg·L−1 6‐benzylaminopurine (BAP). Shoot multiplication was widely affected by the kind and concentration of PGRs, and the subculturing of in vitro regenerated shootlets on fresh medium. After incubation for 4 weeks at optimum BAP concentration, cultures were transferred to secondary medium with BAP (optimized concentration) supplemented with different auxins (indole acetic acid, indole butyric acid, and naphthalene acetic acid [NAA]). Murashige and Skoog medium enriched with 2.0 mg·L−1 BAP showed the highest shoot induction response (83% ± 3.61%) with mean shoot number (4.67 ± 1.45) and shoot length of 4.33 ± 1.45 cm. Growth medium fortified with 1.0 mg·L−1α‐ NAA exhibited maximum rhizogenesis with 4.33 ± 0.88 roots and average root length as 5.50 ± 0.76 cm from regenerated B. amplexicaulis shoots. Acclimatized plants of B. amplexicaulis showed 90% survival. The projected protocol may serve as a treasured tool for the rapid and large‐scale multiplication of elite B. amplexicaulis and for germplasm conservation to ensure continuous supply of this plant amid the increasing demand.

Euonymusfortunei polysaccharides (EFPs) have not been extensively investigated yet in terms of their extraction and biological activity. The orthogonal experimental design was employed in this study to evaluate the optimum yield of EFPs. A maximum yield of 2.63 ± 0.23% was attained using material-liquid ratios of 60 mL/g, extraction temperature of 80°C, ultrasonic power of 144 W, and extraction time of 75 mins. The polysaccharide content reached 53.47 ± 0.31% when deproteinized thrice. An analysis of monosaccharide composition revealed that these polysaccharides consist of Gal, Glc, Man, Fuc, and Rha with a molar ratio of 7.14 ∶ 23.99 ∶ 6.29 ∶ 6.55 ∶ 1.00, respectively, in EFPs. Subsequently, the in vitro scavenging capacities of 2,2-diphenylpicrylhydrazyl (DPPH) and ·OH and superoxide anion radicals, along with the reducing power of EFPs, were studied. Results revealed that EFPs have higher antioxidant activity, particularly ·OH scavenging, as well as reducing power, as compared to Astragalus polysaccharides (ASPs) and Lycium barbarum polysaccharides (LBPs). The Cell Counting Kit-8 (CCK-8) method was used to evaluate the effects of different concentrations of polysaccharides on SKOV3 cell proliferation, and the results revealed their inhibition at concentrations in the range of 200–800 μg/mL. In addition, findings from flow cytometry further confirmed that EFPs blocked the cell cycle at G0/G1 and S phases and induced SKOV3 cell apoptosis. In a word, EFPs could be exploited and used further based on the experimental results from this study.

MiR-378 is abnormally expressed in various cancers, such as hepatocellular carcinoma, renal cell carcinoma, and nonsmall cell lung cancer. Here, we developed a label- and immobilization-free ratiometric homogeneous electrochemical strategy based on exonuclease III (Exo III) for the facile and rapid determination of miR-378. Two 3′-protruding hairpin DNA probes (HPs) are designed in this strategy. Doxorubicin (DOX) and potassium ferrocyanide (Fe2+) were used as label-free probes to produce a response signal (IDOX) and a reference signal (IFe2+) in the solution phase. When no target was present in the solution, the HP was stable, most of the DOX was intercalated in the stem of the HP, and the diffusion rate of DOX was significantly reduced, resulting in reduced electrochemical signal response. When miR-378 was present, double-cycle signal amplification triggered by Exo III cleavage was initiated, ultimately disrupting the hairpin structures of HP1 and HP2 and releasing a large amount of DOX into the solution, yielding a stronger electrochemical signal, which was low to 50 pM. This detection possesses excellent selectivity, demonstrating high application potential in biological systems, and offers simple and low-cost electrochemical detection for miR-378.

There is growing demand for separation of 90Y carrier free from 90Sr coexisting to produce high purity 90Y essential for radiopharmaceutical uses. Thus, in this context the sorption profiles of Y3+ and Sr2+ from aqueous solutions containing diethylenetriaminepenta acetic acid (DTPA), ethylenediaminetetra-acetic acid (EDTA), acetic acid, citric acid, or NaCl onto Chelex-100 (anion ion exchange) solid sorbent were critically studied for developing an efficient and low-cost methodology for selective separation of Y3+ from Sr2+ ions (1.0 × 10−5 M). Batch experiments displayed relative chemical extraction percentage (98 ± 5.4%) of Y3+ from aqueous acetic acid solution onto Chelex-100 (anion ion exchanger), whereas Sr2+ species showed no sorption. Hence, a selective separation of Y3+ from its parent 90Sr2+ has been established based upon percolation of the aqueous solution of Y3+ and Sr2+ ions containing acetic acid at pH 1-2 through Chelex-100 sorbent packed column at a 2 mL min−1 flow rate. Y3+ species were retained quantitatively while Sr2+ ions were not sorbed and passed through the sorbent packed column without extraction. The sorbed Y3+ species were then recovered from the sorbent packed column with HNO3 (1.0 M) at a 1.0 mL min−1 flow rate. A dual extraction mechanism comprising absorption associated to “weak-base anion exchanger” and “solvent extraction” of Y3+ as (YCl6)3− and an extra part for “surface adsorption” of Y3+ by the sorbent is proposed. The established method was validated by measuring the radiochemical (99.2 ± 2 1%), radionuclide purity and retardation factor (Rf = 10.0 ± 0.1 cm) of 90Y3+ recovered in the eluate. Ultimately, the sorbent packed column also presented high stability for reusing 2-3 cycles without drop in its efficiency (±5%) towards Y3+ uptake and relative chemical recovery. A proposed flow sheet describing the analytical procedures for the separation of 90Y3+ from 90Sr2+ using chelating Chelex 100 (anion exchange) packed column is also included.

Traditional Chinese medicine (TCM) serves as a significant adjunct to chemical treatment for chronic diseases. For instance, the administration of Baitouweng decoction (BTWD) has proven effective in the treatment of ulcerative colitis. However, the limited understanding of its pharmacokinetics (PK) has impeded its widespread use. Chinese Bama miniature pigs possess anatomical and physiological similarities to the human body, making them a valuable model for investigating PK properties. Consequently, the identification of PK properties in Bama miniature pigs can provide valuable insights for guiding the clinical application of BTWD in humans. To facilitate this research, a rapid and sensitive UPLC-MS/MS method has been developed for the simultaneous quantification of eleven active ingredients of BTWD in plasma. Chromatographic separation was conducted using an Acquity UPLC HSS T3 C18 column and a gradient mobile phase comprising acetonitrile and water (containing 0.1% acetic acid). The methodology was validated in accordance with the FDA Bioanalytical Method Validation Guidance for Industry. The lower limit of quantitation fell within the range of 0.60–2.01 ng/mL. Pharmacokinetic studies indicated that coptisine chloride, berberine, columbamine, phellodendrine, and obacunone exhibited low Cmax, while fraxetin, esculin, fraxin, and pulchinenoside B4 were rapidly absorbed and eliminated from the plasma. These findings have implications for the development of effective components in BTWD and the adjustment of clinical dosage regimens.

Leontopodium leontopodioides (Willd.) Beauv. (L. leontopodioides.) has been used to treat lung diseases in traditional Chinese medicine (TCM). However, a systematic analysis of its chemical components has not been reported so far. In this study, UPLC-Q-Orbitrap MS and GC-MS were applied to investigate the chemical composition of the water extracts and essential oils of L. leontopodioides. UPLC-Q-Orbitrap MS adopts a heating electrospray ionization source, collecting primary and secondary mass spectrometry data in positive and negative ions, respectively, and uses Compound Discoverer 3.2 software to analyze the collected raw data. As a result, a total of 39 compounds were identified from their high-resolution mass spectra in both positive and negative ionization modes, including 13 flavonoids and their glycosides, 15 phenolic acids, 4 oligosaccharides and glycosides, 4 pentacyclic triterpenoids, and 3 other compounds. Among them, 18 chemical components have not been reported in L. leontopodioides. In the GC-MS section, two common organic solvents (n-hexane and diethyl ether) were used to extract essential oils, and the mass spectra were recorded at 70 eV (electron impact) and scanned in the range of 35∼450 m/z. Compounds were identified using NIST (version 2017), and the peak area normalization method was used to calculate their relative amounts. Finally, 17 components were identified in the volatile oil extracted with n-hexane, accounting for 80.38% of the total volatile oil, including monoterpenoids, phenylpropene, fatty acids, and aliphatic hydrocarbons. In the volatile oil extracted with diethyl ether, 16 components were identified, accounting for 73.50% of the total volatile oil, including phenylpropene, aliphatic hydrocarbons, monoterpenoids, fatty acids, and esters. This study was the first to conduct a comprehensive analysis of the chemical composition of the L. leontopodioides water extract and its essential oil, and a comprehensive chemical composition spectrum was constructed, to lay a foundation for its further pharmacodynamic material basis and quality evaluation.

The advanced and highly functional properties of Al2O3 and NiO nanoparticles promote the widespread use of metal oxides as remarkable electroactive materials for sensing and electrochemical applications. The proposed study describes a comparison of the sensitivity and selectivity of two modified wire membrane sensors enriched with Al2O3 and NiO nanoparticles with conventional wire membranes for the quantification of the antidiabetic drug metformin hydrochloride (MTF). The results show linear relationships of the enriched Al2O3 and NiO nanosensors over the concentration ranges 1.0 × 10−10–1.0 × 10−2 mol L−1 and 1.0 × 10−6–1.0 × 10−2 M for both the modified sensors and the conventional coated wire membrane sensors. The regression equations were EmV = (52.1 ± 0.5) log (MTF) + 729 for enriched nanometallic oxides, EmV = (57.04 ± 0.4) log (MTF) + 890.66, and EmV = (58.27 ± 0.7) log (MTF) + 843.27 with correlation coefficients of 0.9991, 0.9997, and 0.9998 for the aforementioned sensors, respectively. The proposed method was fully validated with respect to the recommendations of the International Union of Pure and Applied Chemistry (IUPAC). The newly functionalized sensors have been successfully used for the determination of MTF in its commercial products.

Urine test strips for urinalysis are a common diagnostic tool with minimal costs and are used in various situations including homecare and hospitalization. The coloration scaled by the naked eye is simple, but it is suitable for semiquantitative analysis only. In this paper, a colorimetric assay is developed based on a smartphone digital camera and urine test strips. Assays of pH, albumin, glucose, and lipase activity were performed as a tool for the diagnosis of aciduria, alkaluria, glycosuria, proteinuria, and leukocyturia. The RGB color channels were analyzed in the colorimetric assay, and the assay exerted good sensitivity, and all the particular diagnoses proved to be reliable. The limits of detection for glucose (0.11 mmol/L), albumin (0.15 g/L), and lipase (2.50 U/μL) were low enough to cover the expected physiological concentration, and the range for pH was also satisfactory. The urine test strips with a camera as an output detector proved applicability to spiked urine samples, and the results were also well in comparison to the standard assays which confirms the practical relevance of the presented findings.

The combined prescriptions of nirmatrelvir/ritonavir and other drugs are limited due to potential drug-drug interactions, so therapeutic drug monitoring (TDM) becomes particularly important. In this study, a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was established for determination of the nirmatrelvir/ritonavir in plasma of patients with COVID-19, providing technical and theoretical support for the TDM. Plasma samples were processed by protein precipitation using acetonitrile, and analytes were separated on an Agilent Poroshell 120 SB-C18 (2.1 × 75 mm, 2.7 μm) column at 35°C. Acetonitrile and 0.1% formic acid in water (52 : 48) were utilized as the mobile phases at a flow rate of 0.3 mL/min. In the multiple reaction monitoring (MRM) mode, nirmatrelvir and ritonavir were monitored using precursor/product ions: m/z 500.2/110.1 and 721.3/296.1, respectively, with selinexor as the internal standard. The linear range of both analytes was 2.0 ng/mL to 5000 ng/mL with good inter- and intraday precision and accuracy, and the recovery was 92.0%–107% for nirmatrelvir and 85.7%–106% for ritonavir. Finally, this method was successfully applied to monitor the exposure levels of nirmatrelvir/ritonavir in plasma samples from hemodialysis patients.

Ziyuglycoside I and ziyuglycoside II are important active components of Sanguisorba officinalis L., which have excellent pharmacological effects, such as antioxidant and anticancer effects. However, the bioavailability of ziyuglycoside I and ziyuglycoside II has not been reported. This work aims to establish a UPLC-MS/MS method to study the pharmacokinetics of ziyuglycoside I and ziyuglycoside II in rats under different administration routes (intragastric and intravenous administration) and to calculate the bioavailability. The concentration of ziyuglycoside I and ziyuglycoside II in rat plasma in the range of 2–2000 ng/mL showed a good linear relationship (r > 0.99). The intra-day accuracies of ziyuglycoside I and ziyuglycoside II ranged from 87% to 110%, and the inter-day accuracies ranged from 97% to 109%. The intra-day precision was less than 15% and the inter-day precision was less than 14%. The matrix effects ranged from 88% to 113%. The recoveries were all above 84%. The developed UPLC-MS/MS method for the determination of ziyuglycoside I and ziyuglycoside II in rat plasma was applied to pharmacokinetics. The bioavailability of ziyuglycoside I and ziyuglycoside II was measured at 2.6% and 4.6%, respectively.

Objective. A sensitive and specific multiplex fluorescence rapid detection method was established for simultaneous detection of SARS-CoV-2, influenza A virus, and influenza B virus in a self-made device within 30 min, with a minimum detection limit of 200 copies/mL. Methods. Based on the genome sequences of SARS-CoV-2, influenza A virus (FluA), and influenza B virus (FluB) with reference to the Chinese Center for Disease Control and Prevention and related literature, specific primers were designed, and a multiplex fluorescent PCR system was established. The simultaneous and rapid detection of SARS-CoV-2, FluA, and FluB was achieved by optimizing the concentrations of Taq DNA polymerase as well as primers, probes, and Mg2+. The minimum detection limits of the nucleic acid rapid detection system for SARS-CoV-2, FluA, and FluB were evaluated. Results. By optimizing the amplification system, the N enzyme with the best amplification performance was selected, and the optimal concentration of Mg2+ in the multiamplification system was 3 mmol/L; the final concentrations of SARS-CoV-2 NP probe and primer were 0.15 μmol/L and 0.2 μmol/L, respectively; the final concentrations of SARS-CoV-2 ORF probe and primer were both 0.15 μmol/L; the final concentrations of FluA probe and primer were 0.2 μmol/L and 0.3 μmol/L, respectively; the final concentrations of FluB probe and primer were 0.15 μmol/L and 0.25 μmol/L, respectively. Conclusion. A multiplex real-time quantitative fluorescence RT-PCR system for three respiratory viruses of SARS-CoV-2, FluA, and FluB was established with a high amplification efficiency and sensitivity reaching 200 copies/mL for all samples. Combined with the automated microfluidic nucleic acid detection system, the system can achieve rapid detection in 30 minutes.

Metformin is an oral biguanides hypoglycaemic agent, which used to lower the blood glucose levels in people with type 2 diabetes mellitus. Many analytical techniques have been used to quantify the drug in different pharmaceutical dosage forms; however, most of these methods have limited throughput in the quality control application. A disposable potentiometric microsensor responsive to metformin has recently been reported. For the first time, herein, this method of analysis has been validated according to IUPAC recommendations and successfully applied in the determination of metformin drug in some dosage form. Different drug formulations of metformin hydrochloride have been collected from the local pharmaceutical stores in Saudi Arabia and analysed using the validated microchip-based method of analysis. Subsequently, the results of this study showed that the validated method was linear, specific, precise, and accurate. The linear range was 1 × 10−1–1 × 10−5 mol L−1 and the correlation coefficient was 0.999. The limit of detection was 2.89 × 10−6 mol L−1, and the limit of quantification was 8.77 × 10−6 mol L−1. This method demonstrated high precision, with an RSD% of less than 2.22%. The accuracy of this method was obtained by comparing the recovery percentage with percentage values less than 5%. The results obtained showed that there was no significant difference between the references, label, and recovery of less than 5%.

This research aims to develop methods for simultaneously determining indomethacin (IND) and nicotinamide (NCT) in binary mixtures, immediate-release capsules, sustained-release capsules, and co-amorphous systems, which were designed in 2021 to improve the solubility, dissolution rate, and stability of the amorphous state of indomethacin. Moreover, this new combination may have also other possible medical benefits. Therefore, there is a need to have simple, sensitive, and precise developed methods for simultaneous quantification analysis of IND/NCT in several different ratios. Three UV-spectrophotometry techniques were deployed: zero-crossing point in the second-order derivative, dual-wavelength in the first-order derivative, and ratio subtraction coupled with spectrum subtraction. The limit of detection and the limit of quantifications (LOD and LOQ) for IND were 0.41 and 1.25, 0.55 and 1.66, and 0.53 and 1.62 μg/mL, respectively, while for NCT were 0.53 and 1.59, 0.38 and 1.14, and 0.36 and 1.08 μg/mL, respectively. All methods were linear at least in the range of 2.5–40.0 μg/mL. All proposed methods were validated according to ICH guidelines and their application on the dosage formulations was carried out. Finally, the proposed methods were compared to a reference method for each IND and NCT, and no significant statistical variance was found.

Radix Dipsaci (RD) is the dry root of the Dipsacus asper Wall. ex DC., which is commonly used for tonifying the kidney and strengthening bone. The purpose of this study was to analyze the difference between raw and salt-processed RD from the chemical composition comprehensively. The fingerprints of raw and salt-processed RD were established by HPLC-DAD to determine the contents of loganin (LN), asperosaponin VI (AVI), caffeic acid (CaA), dipsanoside A (DA), dipsanoside B (DB), chlorogenic acid (CA), loganic acid (LA), isochlorogenic acid A (IA), isochlorogenic acid B (IB), and isochlorogenic acid C (IC). The results showed that after processing with salt, the components with increased contents were LA, CaA, DA, and AVI, and the components with decreased contents were CA, LN, IB, IA, IC, and DB. Then, the chemometric methods such as principal component analysis (PCA) and fisher discriminant analysis (FDA) were used to evaluate the quality of raw and salt-processed RD. In the classification of raw and salt-processed RD, the order of importance of each chemical component was LA > DB > IA > IC > IB > LN > CA > DA > AVI > CaA. These integrated methods successfully assessed the quality of raw and salt-processed RD, which will provide guidance for the development of RD as a clinical medication.

Asthma is a medical condition characterized by inflammation, narrowing, and swelling of a person’s airways, leading to increased mucus production and difficulties in breathing. Topological indices are instrumental in assessing the physical and chemical attributes of these asthma drugs. As resistance to current treatments continues to emerge and undesirable side effects are linked to certain medications, the search for novel and enhanced drugs becomes a top priority. In this study, the examination of 19 distinct asthma medications was focused. In this study, quantitative structure-activity relationship (QSAR) and quantitative structure-property relationship (QSPR) modeling, in combination with multicriteria decision-making (MCDM) technique VIKOR (VIekriterijumsko KOmpromisno Rangiranje) were employed on asthma drugs, to achieve the most favorable rankings for each asthma drug, taking into account their distinct properties. The topological indices employed for QSPR modeling were Randic index, reciprocal Randic index, Zagreb indices, hyper-Zagreb index, harmonic index, geometric arithmetic index, and forgotten index.