Stereoselective Pharmacokinetics and Residue Depletion of Praziquantel and Its Metabolites, 4-Hydroxypraziquantel Enantiomers, in Swine.

Praziquantel (PZQ) is administered as a racemic mixture during swine production to treat parasitic diseases. Despite its widespread application, the pharmacokinetics, residue depletion, bioactivity, and toxicity of PZQ enantiomers in swine remain largely unknown. In this study, a systematic investigation of the pharmacokinetics, tissue distribution, and residue depletion of PZQ, its major metabolites (trans- and cis-4-OH-PZQ), and their enantiomers was conducted in swine. The findings indicated that PZQ was absorbed and metabolized rapidly. In swine plasma, the concentrations of S-PZQ, S-trans-4-OH-PZQ, and R-cis-4-OH-PZQ were higher than those of their respective enantiomers. The three analytes exhibited significant tissue distribution and stereoselectivity in 10 swine tissues. Notably, the two enantiomers of PZQ demonstrated comparable tissue concentrations except in the liver and lung. Moreover, the concentrations of S-trans-4-OH-PZQ and R-cis-4-OH-PZQ were higher than those of their respective enantiomers in the 10 tissues. This study has significant implications for the development of rational dosing strategies, reducing drug usage, and minimizing side effects, as well as accurately assessing the risks associated with PZQ administration and, by extension, other chiral drugs. Furthermore, it lays a theoretical foundation for the future use of the active enantiomer, R-PZQ.

Synthesis and Characterization of Colistin-Functionalized Silica Materials for Rapid Capture of Bacteria in Water.

In this study, a new colistin-functionalized silica gel material (SiO2@NH2@COOH@CST) was synthesized after carboxylation on the surface of amino-modified silica. The main factors affecting the adsorptive properties of the material, such as the types of linkers, the linking methods, the reaction buffers and the particle sizes of carriers, were systematically investigated. The SiO2@NH2@COOH@CST was characterized by means of electron microscopy, Fourier-transform infrared spectroscopy, zeta potential measurements, etc. We demonstrated that the sorbent showed good adsorption of Gram-negative bacteria. The adsorption efficiency of E. coli on SiO2@NH2@COOH@CST was 5.2 × 1011 CFU/g, which was 3.5 times higher than that on SiO2@NH2@COOH, suggesting that electrostatic interactions between SiO2@NH2@COOH@CST and E. coli played a key role. The adsorption was quick, and was reached in 5 min. Both pseudo-first-order and pseudo-second-order kinetic models fit well with the dynamic adsorption process of SiO2@NH2@COOH@CST, indicating that physical adsorption and chemisorption might occur simultaneously during the adsorption process. SiO2@NH2@COOH@CST was successfully applied for the rapid capture of bacteria from water. The synthesized material could be used as a potential means of bacterial isolation and detection.

Simultaneous determination of praziquantel and its main metabolites in the tissues of black goats and their residue depletion.

Praziquantel (PZQ) is a pyrazino-isoquinoline compound with broad spectrum of activity against parasitic trematodes and cestodes, and a key veterinary drug in the parasitic disease control field. However, PZQ residues caused by non-conforming or excessive use in food-producing animals may pose a serious threat to human health. Herein, a simple, sensitive and reproducible LC-MS/MS method was developed for the simultaneous determination of praziquantel and trans- and cis-4-hydroxypraziquantel in black goat tissues to guide the reasonable use of PZQ. The mean recoveries for three target analytes were 71.2 ∼ 117.6%, and the limits of quantification were 1.0 µg/kg. Twenty-five healthy black goats were administered a single dose of praziquantel tablets at a dose of 35 mg/kg of body weight for residue elimination study, The results revealed that praziquantel and 4-hydroxypraziquantel were rapidly depleted in goat tissues and the elimination half-lives did not exceed 1 day in all tissues except for muscle and lung. It provides guidance for the establishment of maximum residue limit of praziquantel in goat.

Surface molecularly imprinted solid-phase extraction for the determination of vancomycin and norvancomycin in milk by liquid chromatography coupled to tandem mass spectrometry.

A simple and sensitive method based on surface molecularly imprinted solid-phase extraction (SMISPE) combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS) was developed to determine the residues of vancomycin (VCM) and norvancomycin (NVCM) in milk samples. The imprinted polymer prepared with teicoplanin as a virtual template can specifically recognize VCM and NVCM. The samples were purified with SMISPE and analyzed by LC-MS/MS in positive ionization mode. The results showed that the VCM and NVCM had a good linear correlation in the range of 0.5 µg/kg to 50 µg/kg. The recoveries of target analytes were from 83.3% to 92.1%, and the limits of quantification were both 1.0 µg/kg. The matrix effects of VCM and NVCM were -11.0% and -3.43%, respectively. The proposed method can efficiently eliminate the interference from matrix compounds and reduce baseline noise, which is useful for the monitoring of the residues of VCM and NVCM in milk samples.

Simultaneous Determination of Multiple Polypeptide Antibiotics Residues in Lake Water by Lyophilization Combined with Liquid Chromatography-Tandem Mass Spectrometry.

It is significant to develop a method for the simultaneous determination of multiple polypeptide antibiotics residues in lake water because of the emergence of multidrug-resistant microorganisms in water. A sensitive, eco-friendly and simple method was developed for the determination of multiple polypeptide antibiotics, including vancomycin, teicoplanin, polymyxin B, colistin and bacitracin A in lake water using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Water samples were lyophilized to enrich them after adjusting the pH to 3. Then, 80% methanol in water containing 0.1% formic acid was used to reconstitute the residues for LC-MS/MS analysis. The results showed that target compounds were well separated and detected under the optimum instrumental conditions. The limits of detection and the limits of quantification of polypeptide antibiotics were in the range of 0.01 - 0.1 and 0.02 - 0.2 ng mL-1, respectively. The matrix-matched calibration curves of all compounds were linear in the calibration range of 1 - 200 ng mL-1. At three spiked levels of 0.2 (0.04), 0.4 (0.1) and 1.0 (0.2) ng mL-1 in lake water, the average recoveries of analytes were higher than 70%, except for teicoplanin, with relative standard deviations of less than 20%. Compared with other common sample pretreatment methods, the lyophilization process is simpler and more eco-friendly, achieving the simultaneous detection of multiple polypeptide antibiotics in lake water. The developed method is successfully applied to the routine monitoring of polypeptide antibiotics residues in lake water.

Preparation of surface molecularly imprinted polymer and its application for the selective extraction of teicoplanin from water.

In this study, a new surface molecularly imprinted polymer (SMIP) of teicoplanin (TEC) was prepared in an aqueous solution using amino-modified silica gel as a carrier. The molar ratio of the template molecule, functional monomer and cross-linker in the optimized synthesis system was 1 : 15 : 40. The structure and morphology of SMIP were characterized by Fourier-transform infrared spectra and scanning electron microscopy, respectively. It was shown that the silica gel modified with different active groups; the type and structure of functional monomers have a great influence on the specificity of SMIP. The SMIPs synthesized from a series of methacrylic acid and its hydroxylalkyl esters as functional monomers have good specificity for TEC. The results of static adsorption experiments showed that the adsorption capacity of SMIP was 6.5 times that of non-molecularly imprinted polymer, which were 152.6 mg g-1 and 23.6 mg g-1, respectively, indicating that SMIP had a larger affinity for TEC. Finally, the SMIP was successfully used as a dispersive solid-phase extraction adsorption material to selectively extract and enrich TEC from the water sample. The limit of detection of the proposed liquid chromatographic method for TEC was 5 µg L-1.

Pharmacokinetics, Activity, and Residue Elimination of R- and S-Diclazuril in Broiler Chickens.

Diclazuril (DIC) is widely used as a racemic mixture to prevent and treat coccidiosis in farm animals, while the pharmacokinetics, bioactivity, and toxicity of DIC enantiomers are not known at all. This study first established a simple, sensitive, and reliable liquid chromatography tandem mass spectrometry method for separation of R-DIC and S-DIC and their analyses. Then, it was applied to investigate the stereoselective pharmacokinetics and residual elimination of individual enantiomers, and their anticoccidial activity was also evaluated in broiler chickens. The results indicated that the area under the concentration-time curve (AUC) and elimination half-life (t1/2ß) were significantly different (p < 0.05) for two enantiomers in chicken plasma. The AUC and t1/2ß of S-DIC were approximately 2 and 1.4 times those of R-DIC, respectively. The residual elimination of DIC enantiomers in chicken tissues was also stereoselective. The concentrations of S-DIC in chicken muscle and liver were greater than those of R-DIC, and it is the opposite in the kidney. There was no significant difference (p > 0.05) in the anticoccidial activity of racemate and enantiomers when a single enantiomer in feed was added above 0.5 mg kg-1. However, the anticoccidial activity of R-DIC (0.25 mg kg-1) was significantly higher (p < 0.05) than that of S-DIC (0.25 mg kg-1) in the diet. It should be mentioned that in chicken small intestine and cecum, the enantiomerization rate of each enantiomer in the infection group was faster than that in the uninfected group.

Analysis of Nosiheptide in Food Animal Tissues via Its Unique Degradation Product by Liquid Chromatography-Tandem Mass Spectrometry after Alkaline Hydrolysis.

Very weak signals of fragment ions of nosiheptide could be observed using liquid chromatography-tandem mass spectrometry. The preparation of 4-hydroxymethyl-3-methyl-1H-indole-2-carboxylic acid (HMIA), a specific fragment of nosiheptide, by alkaline hydrolysis is described. HMIA showed a good mass spectrometric signal in negative electrospray ionization mode. In the new method, the nosiheptide residue in muscle tissue was hydrolyzed with sodium hydroxide aqueous solution; this was followed by cleanup using mixed mode cartridges. Identification and quantification of nosiheptide were carried out by analyzing HMIA in hydrolysate of muscles. Nosiheptide showed a good linear relationship (r > 0.996) in the calibration range of 2-500 µg/kg, and a low limit of quantification of 2 µg/kg was obtained in swine, chicken, and fish muscles. Recoveries of nosiheptide from spiked muscle samples were 85-108% with relative standard deviations less than 10%. The proposed method was successfully applied for the detection of the nosiheptide residue in medicated animal tissues samples.

Determination of residual enantiomers of diclazuril in chicken edible tissues by high performance liquid chromatography.

A convenient, simple, selective and reliable method was established for separating diclazuril enantiomers and detecting their residues in chicken edible tissues by using high-performance liquid chromatography. The potential effects of chiral column, mobile phase and column temperature on chiral separation of racemic diclazuril were evaluated. Average recovery rates of R-diclazuril and S-diclazuril in three spiking levels ranged from 84.3% to 109.5%, and the relative standard deviations were <15.8%. The limits of quantification of two enantiomers were all 25 ng g-1 in all chicken tissues. The method proposed was successfully applied to monitor distributions and residue elimination of diclazuril enantiomers in chicken muscle, liver, kidney and fat following oral administration. There are no obvious differences (p > 0.05) between R-diclazuril and S-diclazuril in the same tissue for each sampling time. The elimination rates in liver were the fastest and the residual time in kidney was the longest. These results can help further evaluate pharmokinetics, pharmodynamics and toxicity of each enantiomer of diclazuril in food-producing animals.