Abstract:
:Tryptophan (Trp) oxidation in proteins leads to a number of events, including changes in color, higher order structure (HOS), and biological activity. We describe here a number of new findings through a comprehensive characterization of 6 monoclonal antibodies (mAbs) following selective oxidation of Trp residues by 2,2'-azobis(2-amidinopropane) dihydrochloride. Fluorescence spectroscopy, in combination with second derivative analysis, demonstrates that the loss of Trp fluorescence intensity is a sensitive indicator of Trp oxidation in mAbs. Size-exclusion chromatography with UV and intrinsic Trp fluorescence detection was demonstrated to be a useful method to monitor Trp oxidation levels in mAbs. Furthermore, the Trp oxidation levels measured by size-exclusion chromatography with UV and intrinsic Trp fluorescence detection were found to be in agreement with the values obtained from tryptic peptide mapping by liquid chromatography with mass spectrometric detection and correlate with the total solvent accessible surface area of the exposed Trp residues from in silico modeling. Finally, near-UV circular dichroism and Raman spectroscopy were used to evaluate the impact of Trp oxidation on HOS and identify specific oxidation products, respectively. This work demonstrates that protein HOS is altered on Trp oxidation in mAbs and multiple spectroscopic markers can be used to monitor the molecule-dependent Trp oxidation behavior.
journal_name
J Pharm Scijournal_title
Journal of pharmaceutical sciencesauthors
Barnett GV,Balakrishnan G,Chennamsetty N,Hoffman L,Bongers J,Tao L,Huang Y,Slaney T,Das TK,Leone A,Kar SRdoi
10.1016/j.xphs.2018.12.027subject
Has Abstractpub_date
2019-06-01 00:00:00pages
1944-1952issue
6eissn
0022-3549issn
1520-6017pii
S0022-3549(19)30006-1journal_volume
108pub_type
杂志文章abstract::A method to determine the adherence of drugs to the esophagus was developed using isolated swine esophagi. A number of types of tablets and capsules (e.g., of doxycycline) were tested. The results showed that the tendency of products to adhere to the esophagus can be regulated by pharmaceutical properties. It was conc...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600710904
更新日期:1982-09-01 00:00:00
abstract::The influence of hepatic uptake and efflux, which includes passive diffusion and transporter-mediated component, on drug distribution volumes [steady-state volume of distribution (V(ss)) and terminal volume of distribution (V(β))], mean residence time (MRT), clearance, and terminal half-life is considered using a simp...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.22696
更新日期:2011-11-01 00:00:00
abstract::Die filling is a critical process step during tablet production as it defines the tablet weight. Achieving die fill consistency during production of mini-tablets, tablets with diameters ≤6 mm, is considerably more challenging. Although die filling in rotary presses had been studied in relation to the feed paddle desig...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1016/j.xphs.2018.09.005
更新日期:2019-03-01 00:00:00
abstract::Diazepam (1), a hypnotic and anxiolytic drug in worldwide use, formed an intermediate product in a mixture of ethanol and sodium hydroxide ([NaOH] > or = 1 M). The intermediate product slowly decomposed to form 2-(methylamino)-5-chlorobenzophenone imine (2) and 2-(methylamino)-5-chlorobenzophenone (3). The amount of 2...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1021/js9504245
更新日期:1996-07-01 00:00:00
abstract::The present study was carried out to investigate the blood-to-retina transport of nicotine across the inner blood-retinal barrier (BRB). Using the in vivo vascular injection method, the blood-to-retina influx clearance of nicotine across the BRB was determined as 131 μL/(min?g retina), which is much higher than that o...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.24453
更新日期:2015-09-01 00:00:00
abstract::Nanoparticle tracking analysis (NTA) obtains particle size by analysis of particle diffusion through a time series of micrographs and particle count by a count of imaged particles. The number of observed particles imaged is controlled by the scattering cross-section of the particles and by camera settings such as sens...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1016/j.xphs.2017.12.016
更新日期:2018-05-01 00:00:00
abstract::Membrane permeation enhancers have received significant attention in recent years for enabling the oral absorption of poorly permeable drug molecules. In this study, we investigated the ability of His-Ala-Val (HAV) and Ala-Asp-Thr (ADT) peptides derived from the extracellular-1 (EC1) domain of E-cadherin proteins to i...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1016/j.xphs.2020.12.018
更新日期:2020-12-23 00:00:00
abstract::The objective of the current study was to evaluate the performance of Raman and near-infrared (NIR) techniques combined with chemometrics in characterizing the critical quality attributes of brompheniramine (BP)-tannate complexes. Seven complexes were prepared and evaluated for chemical interactions, solubilities, dis...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.23030
更新日期:2012-04-01 00:00:00
abstract::In relation to drug release properties the lateral and rotational mobility of two drugs and one drug mimic in photopolymerized poly(ethylene glycol) diacrylate (PEGDA) networks were investigated by nuclear magnetic resonance as a function of the network cross-link density and temperature. The network mesh size affects...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.21251
更新日期:2008-08-01 00:00:00
abstract::Bacmecillinam is an amdinocillin prodrug designed to be easily hydrolyzed in biological materials, so special procedures were developed for the collection of blood specimens. Whole blood was collected in tubes containing bacampicillin as an adsorption inhibitor and kept at -70 degrees; the extracting solvent, hexane-m...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600711018
更新日期:1982-10-01 00:00:00
abstract::The objective of this study was to identify the important factors that determine plasma concentrations of diphenhydramine (DPHM) in the mother and the fetus after maternal as well as fetal steady-state drug administration. Inter-relationships were evaluated between maternal and fetal placental and nonplacental clearan...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1021/js990244l
更新日期:1999-12-01 00:00:00
abstract::The development of an ocular dosage form containing xanthan gum and capable of interacting with mucin in the precorneal area is a challenge. The polymer concentration that can be applied is restricted because of the limited patient acceptability of highly viscous preparations. The precorneal mucin concentration is low...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.10106
更新日期:2002-04-01 00:00:00
abstract::Magnetic resonance imaging (MRI) with chemical shift resolution is a recent extension of MRI and it provides information about species resolved molecular transport on the macroscopic scale in complex systems. In this contribution, we show that by using this novel method, one can predict the behavior of drug and food m...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.20749
更新日期:2007-02-01 00:00:00
abstract::The effects of chlorpromazine, prochlorperazine, and trifluoperazine on the pressor actions of serotonin, angiotensin, and bradykinin in the perfused vessels of full-term human placentas were investigated. A significant inhibition of the effect of serotonin was observed with trifluoperazine and chlorpromazine but not ...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600651020
更新日期:1976-10-01 00:00:00
abstract::The expression of carboxylesterase (CES) and the transdermal movement of an ester prodrug were studied in rat skin. Ethyl-fexofenadine (ethyl-FXD) was used as a model lipophilic prodrug that is slowly hydrolyzed to its parent drug, FXD (MW 502). Among the CES1 and CES2 isozymes, Hydrolase A is predominant in rat skin ...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.24648
更新日期:2016-02-01 00:00:00
abstract::The kinetics of acetylation of alcohols by acetyl chloride and acetic anhydride, with N-methylimidazole as the catalyst, were studied in acetonitrile solution at 25 degrees; some measurements were also made with 4-dimethylaminopyridine as the catalyst. The acetic anhydride-N-methylimidazole system proceeds entirely by...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600710503
更新日期:1982-05-01 00:00:00
abstract::A high-performance liquid chromatographic method has been developed for the simultaneous determination of azobenzene and hydrazobenzene in phenylbutazone and sulfinpyrazone raw materials and formulations. The drug raw material or formulation is shaken with 1N NaOH and n-hexane and centrifuged. The n-hexane layer is in...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600721032
更新日期:1983-10-01 00:00:00
abstract::The physical stability of an immunoglobulin G4 monoclonal antibody (mAb) upon dilution into intravenous (i.v.) bags containing 0.9% saline was examined. Soluble aggregates and subvisible particles were observed by size-exclusion high-performance liquid chromatography (SE-HPLC) and light obscuration when formulated wit...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.23224
更新日期:2012-10-01 00:00:00
abstract::To explore the possibility of cyclodextrin click clusters (CCCs) as a new cyclodextrin-based excipient, we prepared three different CCCs; heptakis{6-(4-hydroxymethyl-1H-[1,2,3]triazol-1-yl)-6-deoxy}-β-cyclodextrin (HT-β-CD), heptakis{6-(4-hydroxymethyl-1H-[1,2,3]triazol-1-yl)-6-deoxy}{2,3-di-O-methyl}-β-cyclodextrin (...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.24107
更新日期:2014-10-01 00:00:00
abstract::Numerous case reports have documented that phenylpropanolamine (PPA) stimulates the central nervous system with symptoms ranging from anxiety and hallucinations to grand mal seizures produced by overdoses. Most of these reports have occurred following concomitant use of caffeine which in high doses is known to cause s...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600781203
更新日期:1989-12-01 00:00:00
abstract::Current drug level predictions in nonlinear pharmacokinetics are based on specific pharmacokinetic models in contrast to the model-independent (structureless), dose-linearity, and superposition principles used in linear pharmacokinetics. Such model-dependent methods may not provide reliable predictions due to their in...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600730614
更新日期:1984-06-01 00:00:00
abstract::Various novel diesters of pilocarpic acid were synthesized and evaluated as prodrug forms for pilocarpine with the aim of improving the ocular delivery characteristics of the drug. The pilocarpic acid monoesters previously studied cyclized spontaneously to pilocarpine in aqueous solution and although they showed enhan...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600750811
更新日期:1986-08-01 00:00:00
abstract::Drug stability studies are expensive and time consuming. Multiple batches are studied to ensure that a product will consistently remain within specifications for its entire expiration dating period. Some of these studies involve the same drug products in similar packages or in multiple strengths. Application of sound ...
journal_title:Journal of pharmaceutical sciences
pub_type: 指南,杂志文章
doi:10.1002/jps.2600841112
更新日期:1995-11-01 00:00:00
abstract::The assay of suppositories containing pentobarbital and/or pyrilamine in a water-soluble polyethylene glycol base by high-pressure liquid chromatography is described. No extraction is required. The suppository is dissolved in the mobile phase. This solution is diluted with an internal standard stock solution containin...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600680524
更新日期:1979-05-01 00:00:00
abstract::New dihydropyridine in equilibrium pyridinium salt-type redox carrier systems were developed in which the drug is linked via the ring nitrogen atom of nicotinamide. The rate of oxidation of the dihydropyridine forms, and thus the overall and brain-specific distribution of the corresponding 3-carbamoyl-1-carbamoylalkyl...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600740304
更新日期:1985-03-01 00:00:00
abstract::A column-switching high-performance liquid chromatographic assay combined with a heart-cutting technique and UV detection (LC/LC/UV) was developed to determine ceftibuten, a new oral cephalosporin, in human plasma. Plasma samples were directly injected into the first chromatographic column for sample cleanup and extra...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600810715
更新日期:1992-07-01 00:00:00
abstract::Variability in the time to crystallization is a major technical and economic hurdle in using amorphous solids in dosage forms. It is hypothesized that amorphous solids "age", and that the older they are, the more relaxed they are and the higher the probability of crystallization. At present, there is no method that al...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.10404
更新日期:2003-07-01 00:00:00
abstract::The antimalarial endoperoxides, such as artemisinin, are postulated to exert their potent parasiticidal activity via the formation of reactive intermediates in the iron-rich infected erythrocyte. The in vitro chemical reaction profile of putative endoperoxide antimalarials and ferrous iron is often qualitatively used ...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.20400
更新日期:2005-08-01 00:00:00
abstract::The pKa values of benzoic acid, p-methylbenzoic, and p-aminobenzoic acid (PABA) were determined by potentiometric titration in mixtures of 0-0.5 volume fractions of various cosolvents and water. The differences between the aqueous and semiaqueous pKa values were similar for the three solutes at a particular cosolvent-...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600750217
更新日期:1986-02-01 00:00:00
abstract::The purpose of this study was to develop a nanocarrier system for codelivery of paclitaxel (PTX) and piperlongumine (PL) and investigate the therapeutic potential of improving efficacy and reducing toxicity. PTX and PL were formulated into poly lactic-co-glycolic acid and D-α-tocopheryl polyethylene glycol succinate v...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1016/j.xphs.2017.05.027
更新日期:2017-10-01 00:00:00