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Current Pharmaceutical
Analysis
ISSN: 1573-4129
Current Pharmaceutical
Analysis
Volume 3, Number 2, May 2007
Contents
Biological and Biochemical Assays to Ensure the Quality
and Safety of Plasma-Derived Products: Factor VIII Concentrates
Pp. 83-94
Miryana Radosevich and Thierry Burnouf
[Abstract]
Recent Advances in Chromatographic Methods to Detect
Drugs of Abuse in Alternative Biological Matrices
Pp. 95-109
Carolina D.R. de Oliveira, Marli Roehsig, Rafael M. de
Almeida, Willian L. Rocha and Mauricio Yonamine
[Abstract]
Analytical Methods for the Characterisation of Multifunctional
Polymers for Oral Drug Delivery Pp. 111-116
Martin Werle, Yung T. Hsu, Fu C. Chang and Chen H. Lee
[Abstract]
Hyaluronan Determination: Biological Significance
& Analytical Tools Pp. 117-128
Christina J. Malavaki, Ioannis Kanakis, Achilleas D. Theocharis,
Fotini N. Lamari and Nikos K. Karamanos
[Abstract]
The Need for Real-Time Measurement of Lung Injury
in Developing an Effective Treatment for Pulmonary Emphysema
Pp. 129-132
Jerome O. Cantor
[Abstract]
Induction of Adhesion Molecule Expression in Vascular
Endothelial Cells by Oxidized Low-Density Lipoprotein: Pharmaceutical,
Biochemical and Clinical Applications Pp. 133-140
Masaaki Matsumoto, Mitsunori Ikeda and Hajime Kodama
[Abstract]
Osteryoung Square Wave Voltammetric Determination
of Phenazopyridine Hydrochloride in Human Urine and Tablet
Dosage Forms Based on Electrochemical Reduction at Carbon
Paste Electrode Pp. 141-145
[Abstract]
Proteases from South American Snake Venoms Affecting
Fibrinolysis Pp. 147-157
Eladio F. Sanchez and Steve Swenson
[Abstract]
Abstracts
[Back to top]
Biological and Biochemical Assays to Ensure the Quality and
Safety of Plasma-Derived Products: Factor VIII Concentrates
Miryana Radosevich and Thierry Burnouf
The manufacture of coagulation Factor VIII concentrates fractionated
from human plasma is subjected to a set of stringent quality
control tests and quality assurance procedures. These requirements
apply to all stages of product development and production,
from the selection and quality control of the starting plasma
source material to the purification, viral inactivation, storage
and distribution phases of the final product in its pharmaceutical
form. The present review addresses the major in-vitro and
in-vivo analytical methods important to assess the potency,
quality, and safety of coagulation Factor VIII products and
to detect the presence of unwanted contaminants such as proteolytic
enzymes and endotoxins.
[Back to top]
Recent Advances in Chromatographic Methods to Detect
Drugs of Abuse in Alternative Biological Matrices
Carolina D.R. de Oliveira, Marli Roehsig, Rafael M. de
Almeida, Willian L. Rocha and Mauricio Yonamine
In recent years, many studies have been developed with the
aim of improving drug detection in both conventional specimens
and alternative biological matrices. A large number of drug
abuse studies, forensic toxicology analyses, drugs in the
workplace and even in doping control in sports activities
related to drug detection in biological samples have been
reported in the literature. The interest in the development
and optimization of analytical techniques to detect drugs
of abuse in different specimens is explained by the several
possibilities and information that they can provide. Conventional
samples such as urine and blood and more recently, saliva
and sweat, are of fundamental importance whenever recent exposure
to drugs is under investigation. Human keratinized tissues
such as hair and nails are especially important for obtaining
data of chronic long-term exposure with the great advantage
of being collected in a non-invasive way. Meconium can be
a useful biological sample to evaluate fetal drug exposure
following maternal drug use. This paper reviews chromatographic
procedures for determination of amphetamines, cannabinoids,
opiates, nicotine, cocaine and alcohol in alternative biological
matrices. Gas chromatographic and liquid chromatographic procedures
with different detectors (including mass spectrometry) and
sample preparation techniques such as liquid-liquid extraction
(LLE), solid phase extraction (SPE) and solid phase microextraction
(SPME) were considered.
[Back to top]
Analytical Methods for the Characterisation of Multifunctional
Polymers for Oral Drug Delivery
Martin Werle, Yung T. Hsu, Fu C. Chang and Chen H. Lee
Multifunctional polymers are highly promising auxiliary agents
for the oral delivery of a broad variety of drugs. The main
features of multifunctional polymers include controlled release,
mucoadhesive, cohesive and permeation enhancing properties
and enzyme as well efflux pump inhibitory properties. Within
the current review, the most important multifunctional polymers
for oral drug delivery as well as various analytical methods
including the rotating cylinder method, tensile studies, confocal
laser scanning microscopy, permeation studies, and also enzyme
and efflux pump inhibition studies are discussed.
[Back to top]
Hyaluronan Determination: Biological Significance
& Analytical Tools
Christina J. Malavaki, Ioannis Kanakis, Achilleas D. Theocharis,
Fotini N. Lamari and Nikos K. Karamanos
Hyaluronic acid is a glycosaminoglycan, which is one of the
main components of the extracellular matrix, contributes significantly
to cell proliferation and migration, and is involved in many
physiological and pathological biologic processes, such as
the progression of some malignant tumors. Therefore, the determination
of its amounts may be of use for monitoring the progress of
some diseases and/or as prognostic/diagnostic marker. Hyaluronan
has been used for the therapy of osteoarthritis, for ophthalmic
and cosmetic surgeries, and is under investigation for numerous
other diseases. In this review, after a short introduction
to hyaluronan structure and biologic roles, the electrophoretic,
chromatographic and solid-phase assays used for determination
of its concentration in biologic samples and in drug formulations
are presented.
[Back to top]
The Need for Real-Time Measurement of Lung Injury
in Developing an Effective Treatment for Pulmonary Emphysema
Jerome O. Cantor
Chronic obstructive pulmonary disease (COPD) is characterized
by diffuse inflammation of the airways and parenchyma of the
lung. In its most devastating form, the disease produces widespread
emphysematous changes in the lung, characterized by dilatation
and rupture of alveoli, marked impairment of gas exchange,
and eventual respiratory failure. The development of therapeutic
agents for COPD, and pulmonary emphysema in particular, has
been hampered by the lack of clinical or biochemical tests
which can rapidly and reliably determine drug efficacy. The
only recognized endpoint for evaluating new treatments, pulmonary
function studies, may take years to detect a significant effect.
This delay is due to the fact that pulmonary emphysema progresses
at a relatively slow rate, and the available methods for measuring
the loss of lung function are not particularly sensitive.
Since elastic fiber degradation is an important feature of
pulmonary emphysema, the authors propose measuring specific
breakdown products of these fibers in sputum as a more immediate
means of monitoring therapeutic interventions. In addition
to facilitating rapid evaluation of new forms of treatment
for pulmonary emphysema, this assay might also prove to be
a useful screening procedure for persons who smoke or otherwise
have a greater than normal risk of developing this disease.
[Back to top]
Induction of Adhesion Molecule Expression in Vascular
Endothelial Cells by Oxidized Low-Density Lipoprotein: Pharmaceutical,
Biochemical and Clinical Applications
Masaaki Matsumoto, Mitsunori Ikeda and Hajime Kodama
Interactions between lipoproteins and vascular endothelium
are considered to be a central component of the pathogenesis
of atherosclerosis and cutaneous xanthomas. It is widely accepted
that the binding of oxidized low-density lipoprotein to cell
membrane receptors activates an intracellular signal transduction
pathway that produces adhesion molecules on the surface of
endothelial cells. Circulating monocytes adhere to these molecules
and subsequently migrate across the cell membrane into the
lesions. Growing evidence indicates that the mechanisms of
adhesion molecule expression vary depending on the oxidation
process of low-density lipoprotein and the organ specificity
of the endothelial cells. This review summarizes recent studies
involving the induction of adhesion molecule expression in
vascular endothelial cells by oxidized low-density lipoprotein,
with special attention to the pharmaceutical, biochemical,
and clinical applications of this process.
[Back to top]
Osteryoung Square Wave Voltammetric Determination
of Phenazopyridine Hydrochloride in Human Urine and Tablet
Dosage Forms Based on Electrochemical Reduction at Carbon
Paste Electrode
An electroanalytical method was developed for the direct quantitative
determination of phenazopyridine hydrochloride (PAP) or in
other words, pyridium, in spiked human urine and tablet dosage
forms. The electrochemical reduction and determination of
PAP were carried out at carbon paste electrode (CPE) in various
aquaeous solution in the pH range of 0.5-12.30 by (CV) and
osteryoung square wave voltammetry (OSWV). The best results
were obtained for the quantitative determination of PAP by
OSWV method in 0.5 mol L-1
sulfuric acid at about pH 0.51. The peak current and peak
potential depend on pH and scan rate were studied. The diffusion
controlled nature of the peak was established. This electroanalytical
procedure made it possible to determine PAP in the concentration
range 2.5x10-8-2.5x10-6
mol L-1. Limit of detection
(LOD) and limit of quantification (LOQ) were obtained as 7.5x10-9
and 2.5x10-8 mol L-1
respectively. Precision and accuracy of the developed method
were checked by recovery studies in spiked urine and tablet
dosage forms.
[Back to top]
Proteases from South American Snake Venoms Affecting
Fibrinolysis
Eladio F. Sanchez and Steve Swenson
Venoms of the viperidae (vipers and pit vipers) snakes
are rich sources of proteinases which render fibrinogen incoagulable
and solubilize fibrin. Many of these compounds have profound
effects (stimulating or inhibiting) on the hemostatic mechanism,
including, blood coagulation cascade, fibrinolysis, hypotension,
vascular integrity and platelet function. The lethality of
a venom often appears to be due to the combined action of
several of these components, but severe consequences are frequently
connected with hemostatic disorders. Viperid snake bite accidents
in human and other large animals are characterized by localized
or generalized bleeding and or thrombotic sequelae. This review
is focused on the structural properties and features of a
number of South American snake venom enzymes possessing clearly
defined (pro)fibrinolytic activity. Under physiological conditions
the venom proteins active on the plasminogen/fibrinolytic
system can be grouped into two main categories: 1) direct-acting
fibrinolytic endoproteinases which are related in amino acid
sequence to the major family of metalloproteinases known as
the metzincins. The members of this group are zinc-containing
metalloproteinases (SVMPs) varying in size from 20 to 100
kDa and often more than one example is present in the same
venom. 2) serine proteinases which specifically activate plasminogen
into plasmin, and contain at least one catalytic domain structurally
similar to trypsin. A number of these proteinases have been
isolated and their mechanism of action established. Both direct
and indirect endoproteinases on their own are practically
nontoxic; however, they may act synergistically with other
factors aggravating their toxic effects. Moreover, these proteinases
are characterized by a relatively high degree of substrate
specificity and resistance to physiological inhibitors. Indeed,
some of these venom components are thought to hold promise
as agents for medical applications in the field of thrombosis
and diagnosis, or to hold the key for the design of pharmaceuticals.
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