Superiority of the S,S conformation in diverse pharmacological processes: Intestinal transport and entry inhibition activity of novel anti-HIV drug lead

Fanous, Joseph; Swed, Avi; Joubran, Salim; Hurevich, Mattan; Britan-Rosich, Elena; Kotler, Moshe; Gilon, Chaim; Hoffman, Amnon

doi:10.1016/j.ijpharm.2015.09.027

Cited by 3 publications

(1 citation statement)

References 5 publications

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“…Fick’s Law was applied to calculate the diffusion of proteins in each membrane (eq ). , Where J is the diffusion flux, which can be converted to the change of protein amount in each chamber at the membrane boundary at each chamber side, D eff is the effective diffusion coefficient of protein in membranes, C is the protein concentration, and x is the diffusion distance.…”

Section: Resultsmentioning

confidence: 99%

Diffusion of Protein Molecules through Microporous Nanofibrous Polyacrylonitrile Membranes

Zhao

Zhu

et al. 2021

ACS Appl. Polym. Mater.

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Porous nanofibrous membranes have ultrahigh specific surface areas and could be broadly employed in protein purification, enzyme immobilization, and biosensors with enhanced selectivity, sensitivity, and efficiency. However, large biomolecules, such as proteins, have hindered diffusion behavior in microporous media, significantly reducing the benefits provided by the nanofibrous membranes. The study of protein diffusion in polyacrylonitrile nanofibrous membranes produced under varied humidity and polymer concentration of electrospinning revealed that heterogeneous structures of the nanofibrous membranes possess much smaller effective pore sizes than the measured pore sizes, which significantly affects the diffusion of large molecules through the system though sizes of proteins and pH conditions also have great impacts. Only when the measured membrane pore size is at least 1000 times higher than the protein size, the diffusion behavior of the protein is predictable in the system. The results provide insights into the design and applications of proper nanofibrous materials for improved applications in protein purification and immobilizations.

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Section: Resultsmentioning

confidence: 99%

Diffusion of Protein Molecules through Microporous Nanofibrous Polyacrylonitrile Membranes

Zhao

Zhu

et al. 2021

ACS Appl. Polym. Mater.

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Enantioselective LC‐MS/MS method for the determination of cloperastine enantiomers in rat plasma and its pharmacokinetic application

et al. 2020

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Cloperastine is a central antitussive used to reduce the frequency and intensity of coughing on a short‐term basis. In this study, a reliable chiral LC‐MS/MS technology has been developed for the quantification of cloperastine enantiomers in the rat plasma. Carbinoxamine was selected as the internal standard. The enantioseparation of cloperastine was performed on a Chiralpak IA column with a mobile phase composed of acetonitrile‐water‐ammonium hydroxide (80:20:0.1, v/v/v) at a flow rate of 0.6 mL/min. Cloperastine enantiomers were detected by mass spectrometry in multiple reaction monitoring mode with a positive electrospray ionization source. The method was validated over the linear concentration range of 0.05 to 10.0 ng/mL (5.0 × 10−4 ng to 0.10 ng) for both enantiomers. The lower limit of quantification (LLOQ) for each analyte was determined as 0.05 ng/mL. The relative standard deviations (RSDs) of intraday and interday precision was less than 13.9%, and the relative error (RE) of accuracy ranged from −5.4% to 6.1%, which were within the acceptance criteria. Finally, an application to the stereoselective pharmacokinetics of cloperastine in rats was successfully realized in our assay. The developed method on a commercially available Chiralpak IA column under isocratic mobile phase is advantageous to analyze cloperastine enantiomers in plasma samples collected for enantioselective metabolism or drug interaction studies.

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Enantioselective separation and determination of miconazole in rat plasma by chiral LC–MS/MS: application in a stereoselective pharmacokinetic study

Sun

et al. 2017

Anal Bioanal Chem

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Miconazole has one chiral center, and consists of two enantiomers. In this study, a novel chiral liquid chromatography-tandem mass spectrometry method was developed for enantioselective separation and determination of miconazole in rat plasma. For the first time, the enantioselective pharmacokinetics of miconazole was investigated by the current method. Firstly, attempts were made to separate the enantiomers in reversed-phase mode with a mobile phase that was mass spectrometry compatible. Baseline separation was achieved on a Chiralpak IC column with a mobile phase composed of acetonitrile and aqueous ammonium hydrogen carbonate (5 mM; 80:20, v/v). Data were acquired in multiple reaction monitoring mode with positive electrospray ionization by triple-quadrupole mass spectrometry. Then, overall method validation regarding the linearity, accuracy, precision, extraction recovery, matrix effect, and stability of each enantiomer was performed, and acceptable results were obtained for all of these. Finally, the method developed was applied in an enantioselective pharmacokinetic study of miconazole enantiomers in rats after oral administration of racemic miconazole at doses of 5 and 10 mg/kg. The results demonstrated that (-)-(R)-miconazole had a higher concentration than (+)-(S)-miconazole in plasma, with a ratio of 1.3-1.7 for both doses. This is the first experimental evidence of enantioselective behavior of miconazole in vivo, and provides a reference for clinical practice and encourages further research into miconazole enantioselective metabolism and drug interactions. Graphical Abstract A stereoselective pharmacokinetic study of the miconazole enantiomers was investigated using a novel chiral liquid chromatography-tandem mass spectrometry method. Baseline separation was achieved on Chiralpak IC column, and Chiralcel OJ column was used to collect single enantiomer. A significant difference between the two enantiomers was observed in view of the plasma concentration.

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Superiority of the S,S conformation in diverse pharmacological processes: Intestinal transport and entry inhibition activity of novel anti-HIV drug lead

Cited by 3 publications

References 5 publications

Diffusion of Protein Molecules through Microporous Nanofibrous Polyacrylonitrile Membranes

Diffusion of Protein Molecules through Microporous Nanofibrous Polyacrylonitrile Membranes

Enantioselective LC‐MS/MS method for the determination of cloperastine enantiomers in rat plasma and its pharmacokinetic application

Enantioselective separation and determination of miconazole in rat plasma by chiral LC–MS/MS: application in a stereoselective pharmacokinetic study

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