Abstract：
:The ability to produce and isolate relatively pure amounts of relevant degradation products is key to several aspects of drug product development: (a) aid in the unambiguous structural identification of such degradation products, fulfilling regulatory requirements to develop safe formulations (International Conference on Harmonization Q3B and M7); (b) pursue as appropriate safety evaluations with such material, such as chronic toxicology or Ames testing; (c) for a specified degradation product in a late-stage regulatory filing, use pure and well-characterized material as the analytical standard. Producing such materials is often a resource- and time-intensive activity, either relying on the isolation of slowly formed degradation products from stressed drug product or by re-purposing the drug substance synthetic route. This problem is exacerbated if the material of interest is an oxidative degradation product, because typical oxidative stressing (H2O2 and radical initiators) tends to produce a myriad of irrelevant species beyond a certain stress threshold, greatly complicating attempts for isolating the relevant degradation product. In this article, we present reagents and methods that may allow the rapid and selective enrichment of active pharmaceutical ingredient with the desired oxidative degradation product, which can then be isolated and used for purposes described above.
journal_name
J Pharm Scijournal_title
Journal of pharmaceutical sciencesauthors
Nanda KK,Mozziconacci O,Small J,Allain LR,Helmy R,Wuelfing WPdoi
10.1016/j.xphs.2018.10.059subject
Has Abstractpub_date
2019-04-01 00:00:00pages
1466-1475issue
4eissn
0022-3549issn
1520-6017pii
S0022-3549(18)30693-2journal_volume
108pub_type
杂志文章abstract：:A specific, sensitive, rapid, and reproducible analytical GLC method for lidocaine in human plasma, including pharmacokinetic parameters, is described. Aminopyrine is the internal standard. The method was used to study pharmacokinetics in four healthy volunteers following the administration of a lidocaine bolus at a d...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600661007
更新日期：1977-10-01 00:00:00
abstract：:Aggregation of therapeutic monoclonal antibodies has a potential risk of immunogenicity, requiring minimization of aggregate formation. We have developed a fitting formula for antibody aggregation at 40°C based on physicochemical parameters, including colloidal and conformational stabilities. An IgG1 monoclonal antibo...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1016/j.xphs.2019.10.038
更新日期：2020-01-01 00:00:00
abstract：:The elementary osmotic pump is a new delivery system for drugs or other active agents; it delivers the agent by an osmotic process at a controlled rate. Control resides in the: (a) water permeation characteristics of a semipermeable membrane surrounding the formulated agent, and (b) osmotic properties of the formulati...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600641218
更新日期：1975-12-01 00:00:00
abstract：:Iontophoretic transdermal delivery of sumatriptan was investigated in vitro. Among the conditions tested, 0.25 mA/cm2 and low ionic strength (NaCl 25 mM) was the best experimental condition to increase its transport across the skin. The flux increased 385-fold respective to passive diffusion, thus resulting in a trans...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.20447
更新日期：2005-10-01 00:00:00
abstract：:Conjunctiva occupies most of the ocular surface area, and conjunctival permeability affects ocular and systemic drug absorption of topical ocular medications. Therefore, the aim of this study was to obtain a computational in silico model for structure-based prediction of conjunctival drug permeability. This was done b...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1016/j.xphs.2017.04.061
更新日期：2017-09-01 00:00:00
abstract：:The University of British Columbia (UBC) became the first university in Canada to develop a strategy for enhancing global access to its technologies. UBC's University-Industry Liaison Office, in collaboration with the UBC chapter of Universities Allied for Essential Medicines (UAEM), established a mandate and develope...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.21495
更新日期：2009-03-01 00:00:00
abstract：:Clinical lots of recombinant human platelet-activating factor acetylhydrolase (rhPAF-AH) were prepared in a lyophilized formulation. After reconstitution with sterile water for injection to form an aqueous solution (10 mM sodium citrate, 7.5 w/v% sucrose, and 0.1 w/v% Pluronic-F68, pH 6.5), a few visible, slowly growi...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.20237
更新日期：2005-02-01 00:00:00
abstract：:Regional permeability coefficients of 19 drugs with different physicochemical properties were determined using excised segments from three regions of rat intestine: jejunum, ileum, and colon. The results are discussed in relation to the characteristics of the drug, i.e., MW (range 113-1071 Da), pKa, log D (octanol/wat...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1021/js970218s
更新日期：1998-03-01 00:00:00
abstract：:Selected synthetic luteinizing hormone releasing hormone preparations were assayed, and their potencies were determined relative to one sample utilizing primary cultures of enzymatically dispersed rat anterior pituitary cells. Preliminary cell culture experiments indicated that luteinizing hormone releasing hormone ha...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600660319
更新日期：1977-03-01 00:00:00
abstract：:The chemical stability of the novel anticancer agent carzelesin in aqueous buffer/acetonitrile (1:1, v/v) mixtures has been investigated utilizing a stability-indicating reversed-phase high-performance liquid chromatographic assay. The degradation kinetics of carzelesin has been studied as a function of pH, buffer com...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1021/js960005n
更新日期：1996-11-01 00:00:00
abstract：:Lipid-based dose forms, which encompass a wide variety of compositional and functional characteristics, can be advantageously utilized for the formulation of lipophilic drugs. There has been a traditional reluctance to develop lipid-based dose forms due to potential problems of chemical and physical instability, and a...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章,评审
doi：10.1002/1520-6017(200008)89:8<967::aid-jps1>3.0.co
更新日期：2000-08-01 00:00:00
abstract：:High yields of potential glycol metabolites of p-synephrine, epinephrine, octopamine, and normacromerine can be obtained from the readily available monosubstituted and disubstituted acetophenones. The general procedure involves alpha-bromination followed by displacement with acetate ion and reduction with lithium alum...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600750621
更新日期：1986-06-01 00:00:00
abstract：:Evidence is provided for the existence of a second discrete chemical form of meropenem at clinically relevant concentrations prepared from the marketed formulation of the drug. Proton and carbon-13 NMR spectra in D2O, coupled with tandem mass spectroscopy (MS/MS) and cross polarization/magic angle spinning (CP-MAS) NM...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1021/js970370u
更新日期：1998-05-01 00:00:00
abstract：:In the present work, the effect of controlled nucleation on the stability of human growth hormone (hGH) during freeze-drying has been investigated. More specifically, the vacuum-induced surface freezing technique has been compared to conventional freezing, both with and without an annealing step. Size exclusion chroma...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1016/j.xphs.2019.04.014
更新日期：2020-01-01 00:00:00
abstract：:Ambrisentan is a nonsulfonamide, ET(A)-selective endothelin receptor antagonist (ERA) approved for the treatment of pulmonary arterial hypertension (PAH), and tadalafil is a phosphodiesterase type 5 (PDE-5) inhibitor under investigation for treatment of PAH. Due to the potential combination use, the pharmacokinetic (P...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章,随机对照试验
doi：10.1002/jps.21789
更新日期：2009-12-01 00:00:00
abstract：:The tissue:plasma partition coefficients (Kp ) are good indicators of the extent of tissue distribution. Therefore, advanced tissue composition-based models were used to predict the Kp values of drugs under in vivo conditions on the basis of in vitro and physiological input data. These models, however, focus on animal...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.24427
更新日期：2015-06-01 00:00:00
abstract：:Industry experience suggests that g-forces sustained when vials containing protein formulations are accidentally dropped can cause aggregation and particle formation. To study this phenomenon, a shock tower was used to apply controlled g-forces to glass vials containing formulations of two monoclonal antibodies and re...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.24259
更新日期：2015-02-01 00:00:00
abstract：:A physiological flow model was developed for the distribution of sulfathiazole residues in various tissues in swine. The approach was compartmental, in which the compartments and equilibrium constants had physiological meaning. Differential equations were developed, and appropriate parameter values and initial conditi...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600731107
更新日期：1984-11-01 00:00:00
abstract：:The development of multiple drug modalities over the past 20 years has dramatically expanded the therapeutic space for intervention in disease processes. Rather than being alternative therapeutic approaches, these modalities tend to be complimentary both in the scope of target space and the biological mechanisms harne...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1016/j.xphs.2020.09.057
更新日期：2021-01-01 00:00:00
abstract：:The degradation kinetics of gonadorelin were investigated systematically with reversed-phase high-performance liquid chromatography. The stability-indicating properties of this system were checked with photodiode array detection and by comparison with capillary zone electrophoretic analysis. Influences of gonadorelin ...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1021/js9601187
更新日期：1996-10-01 00:00:00
abstract：:Hard gelatin capsule (HGC) shells are widely used to encapsulate drugs for oral delivery but are vulnerable to gelatin cross-linking, which can lead to slower and more variable in vitro dissolution rates. Adding proteolytic enzymes to the dissolution medium can attenuate these problems, but this complicates dissolutio...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1016/j.xphs.2018.08.009
更新日期：2018-12-01 00:00:00
abstract：:In this study, the effects of structurally related organic impurities on the molecular dynamics of amorphous sulfamethazine were evaluated using thermal analysis. Sulfanilamide (SNA), sulfamerazine (SMR), and sulfadimethoxine were used as virtual impurities of sulfamethazine. The amorphous state was prepared in situ i...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1016/j.xphs.2016.12.008
更新日期：2017-04-01 00:00:00
abstract：:The present studies were undertaken to describe the dynamic nature of the degradation and absorption of insulin in the subcutaneous injection site and to develop agents which would stabilize this dosage form. [125I]Insulin with 0.2-U/kg of unlabeled insulin in 10 microliters of aqueous solution was injected subcutaneo...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600720428
更新日期：1983-04-01 00:00:00
abstract：:Literature data relevant to the decision to allow a waiver of in vivo bioequivalence (BE) testing for the approval of immediate release (IR) solid oral dosage forms containing ethambutol dihydrochloride as the only active pharmaceutical ingredient (API) are reviewed. Ethambutol dihydrochloride is a Biopharmaceutics Cl...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.21061
更新日期：2008-04-01 00:00:00
abstract：:This work aimed at establishing a framework to screen and understand the product variability deeming from factors that affect the quality features of cream formulations. As per Quality by Design - based approach, cream quality target profile and critical quality attributes were identified, and a risk assessment analys...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1016/j.xphs.2019.06.006
更新日期：2019-10-01 00:00:00
abstract：:Co-amorphous drug-amino acid systems have gained growing interest as an alternative to common amorphous formulations which contain polymers as stabilizers. Several preparation methods have recently been investigated, including vibrational ball milling on a laboratory scale or spray drying in a larger scale. In this st...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1016/j.xphs.2016.09.027
更新日期：2017-01-01 00:00:00
abstract：:The objective of this study was to investigate product performance of freeze dried l-arginine/sucrose-based formulations under variation of excipient weight ratios, l-arginine counter ions and formulation pH as a matrix to stabilize a therapeutic monoclonal antibody (MAb) during freeze drying and shelf life. Protein a...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.24501
更新日期：2015-07-01 00:00:00
abstract：:Nasal mucosa excised from dogs or rabbits was mounted as a flat sheet in an in vitro chamber. The permeability was assessed by measuring the unidirectional flux of the radiolabeled tracer compounds, water, sucrose, polyethylene glycol, and cholecystokinin octapeptide. The permeability coefficients calculated from the ...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600761206
更新日期：1987-12-01 00:00:00
abstract：:The aim of this study was to characterize the metabolic pathways of 2-methoxyestradiol (2ME2), an investigational anticancer drug. In vitro metabolism studies were performed by incubation of 2ME2 with human liver microsomes under various conditions and metabolite identification was performed using liquid chromatograph...
journal_title：Journal of pharmaceutical sciences
pub_type： 临床试验,杂志文章
doi：10.1002/jps.20837
更新日期：2007-07-01 00:00:00
abstract：:As part of a series of articles in this special issue evaluating model IgG1-Fc glycoforms for biosimilarity analysis, 3 well-defined IgG1-Fc glycoforms (high mannose-Fc, Man5-Fc, and N-acetylglucosamine-Fc) and a nonglycosylated Fc protein (N297Q-Fc) were examined in this work to elucidate chemical degradation pathway...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1016/j.xphs.2015.10.024
更新日期：2016-02-01 00:00:00
