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Current Pharmaceutical
Analysis
ISSN: 1573-4129
Current Pharmaceutical
Analysis
Volume 2, Number 4, November 2006
Contents
Recent Developments in Proteoglycan Purification and
Analysis Pp. 323- 337
Mihaela Didraga, Begona Barroso and Rainer Bischoff
[Abstract]
Third Generation Radiopharmaceuticals for Imaging
and Targeted Therapy Pp. 339-352
Guillermina Ferro-Flores, Consuelo Arteaga de Murphy and
Laura Meléndez-Alafort
[Abstract]
Stable Isotope Dilution Mass Spectrometry Analysis
of Endogenous and Synthetic Corticosteroids for the Pharmacokinetic
and in vivo Metabolic Investigations in Humans Pp.
353-367
Takashi Furuta and Hiromi Shibasaki
[Abstract]
Analysis of Antioxidant as a Therapeutic Agent
for Atherosclerosis Pp. 369-384
Chi Feng Tseng and Simon J.T. Mao
[Abstract]
Novel Advanced Approaches in Sample Preparation
and Analyte Detection for Bioanalysis Pp. 385-404
Georgios A. Theodoridis and Ioannis N. Papadoyannis
[Abstract]
A Review of Process Analytical Technology (PAT)
in the U.S. Pharmaceutical Industry Pp. 405-414
James Munson, C. Freeman Stanfield and Bir Gujral
[Abstract]
Abstracts
[Back to top]
Recent Developments in Proteoglycan Purification and
Analysis
Mihaela Didraga, Begona Barroso and Rainer Bischoff
Proteoglycans are ubiquitous biomolecules in the body
located in the extracellular matrix, on the cell surface and
also within the cells. They contain at least one glycosaminoglycan
(GAG) chain covalently attached to a core protein and may
also present N- or O-linked glycans. The high structural diversity
and distribution relate to the various biological functions
of proteoglycans. In recent years, new members have enlarged
the proteoglycan family and advances in molecular biology
and glycobiology contributed to elucidate more of the biological
functions of proteoglycans. In order to study the structure
of a proteoglycan molecule and relate it to its function (or
dysfunction), its isolation and purification from cell culture
or tissue extracts is necessary. Next to the widely used anion
exchange chromatographic methods, techniques based on lectin
affinity chromatography have created new possibilities to
increase the degree of purity. Introduction of electrospray
ionization (ESI) and matrix–assisted laser desorption-ionization
(MALDI) sources, together with tandem mass spectrometry (MS/MS
or MSn), mark a further important step towards the structural
analysis of glycosaminoglycans. The aim of this review is
to present the most recent advances in proteoglycan purification
and analysis.
[Back to top]
Third Generation Radiopharmaceuticals for Imaging and Targeted
Therapy
Guillermina Ferro-Flores, Consuelo Arteaga de Murphy and
Laura Meléndez-Alafort
Radiopharmaceutical chemistry has addressed the issue
of biomolecular chemistry, and radiopharmaceuticals are unique
in their ability to monitor receptor binding sites and enzymes.
The future of diagnostic and therapeutic nuclear medicine,
to study the in vivo metabolism, is focused on the
use of radiolabeled protein fragments, peptide structures
and DNA chains. These radiolabeled molecules represent a substantial
change in the paradigms of the pharmaceutical development
by employing, as a source of pharmaceuticals, capabilities
of our own body, instead of considering it as a simple test-tube
where strange molecules interact. Research on biomolecules
complexed to radioactive metals, like Tc-99m, Re-188, Lu-177
and Y-90, that do not alter the molecular specificity, is
a topic of world interest in radiopharmaceutical investigations.
Some perspectives and achievements on the preparation and
analysis of main diagnostic and therapeutic radiopharmaceuticals
of the third generation are presented.
[Back to top]
Stable Isotope Dilution Mass Spectrometry Analysis
of Endogenous and Synthetic Corticosteroids for the Pharmacokinetic
and in vivo Metabolic Investigations in Humans
Takashi Furuta and Hiromi Shibasaki
This review article underlines the importance of stable
isotope dilution mass spectrometry analysis of endogenous
and synthetic corticosteroids for the pharmacokinetic and
in vivo metabolic investigations in humans. The multi-labeled
corticosteroids with stable isotopes such as [1,2,4,19-13C4]cortisol,
[1,2,3,4-13C4]cortisol, [1,1,19,19,19-2H5]cortisol,
[9,11,12,12-2H4]cortisol, etc. have
been used not only as analytical internal standard for the
mass spectrometry but as tracer in the pharmacokinetic and
metabolic studies in human in vivo. Stable isotope
dilution analysis of cortisol metabolites (tetrahydrocortisol
(THF), allo-tetrahydrocortisol (allo-THF), tetrahydrocortisone
(THE), and β-hydroxycortisol
(β-OHF))
and synthetic corticosteroids (prednisolone, prednisone, budesonide,
fluticasone, etc.) is also the subject of this review. In
the gas chromatographic mass spectrometric (GC-MS) analysis
of corticosteroids, it is usual to employ derivatives in which
some or all of the original functional groups are protected.
Thermal stabilization of corticosteroids in the analysis has
been achieved most successfully by formation of methoxime-trimethylsilyl
(MO-TMS) derivatives. Bismethylenedioxy-pentafluoropropionyl
(BMD-PFP) derivatives have been developed to simultaneously
measure cortisol, cortisone, and their tetrahydrocorticoid
metabolites (THF, allo-THF, and THE) and/or prednisolone and
prednisone in plasma and urine. Stable isotope tracer methodology
has been applied to the measurements of cortisol production
rate, determination of human urinary cortisol metabolites,
and assessment of in vivo activities of 11β-hydroxysteroid
dehydrogenase (11β-HSD)
in humans. This methodology also has been used for the validity
of endogenous cortisol β-hydroxylation
clearance as a new index for phenotyping the in vivo
cytochrome P450 3A (CYP3A) in humans
[Back to top]
Analysis of Antioxidant as a Therapeutic Agent
for Atherosclerosis
Chi Feng Tseng and Simon J.T. Mao
Research into the oxidation of lipoprotein has yielded
many insights into the underlying process of the development
of atherosclerosis. Oxidative modification of low density
lipoprotein (LDL) has been suggested as an initial step in
the pathogenesis of atherosclerosis. However, up until now,
investigations of antioxidants have mostly focused on three
main dietary antioxidant vitamins (β-carotene,
vitamin C, and vitamin E) and some synthetic compounds. Among
those antioxidants, probucol, a synthetic compound, has been
shown to be an extremely potent and effective antioxidant
in preventing the formation of atherosclerosis in both in
vitro and in vivo studies. The present review
focuses on commonly used analytical methods for measuring
the antioxidant potency and outlines the critical steps on
how to evaluate and design a potent antioxidant agent that
can be used for the intervention of atherosclerosis. We concluded
that an antioxidant should first be targeted and incorporated
into human LDL. Second, the candidate compound should possess
high bioavailability. The rationale and strategy for the analytical
procedures are discussed in this report.
[Back to top]
Novel Advanced Approaches in Sample Preparation
and Analyte Detection for Bioanalysis
Georgios A. Theodoridis and Ioannis N. Papadoyannis
Sample preparation represents a major challenge and a
very important step in the development and application of
an analytical method. It is now widely accepted that sample
preparation is the most time-consuming and often the costliest
step in an analytical process. In addition it is the most
labour-intensive and the most error prone. In the post genome
era new analytical technologies are sought to address the
upcoming needs: proteomics, metabolomics, holistic analytical
approaches, high-throughput screening, biomarker discovery
and drug discovery. Sample preparation is still in certain
cases one of the bottlenecks of the data generation. However
new exciting technologies and developments are continuously
emerging. The present review will try to discuss critically
the status and the limitations of existing methods and highlight
the potential and the advantages of selected novel technologies
for sample preparation and analyte detection. Emphasis is
put on sample preparation methods that are used in bioanalysis
in combination with separation techniques. The review will
try to highlight trends in automation, derivatisation, microextraction
and the implementation of molecular recognition mechanisms
in bioanalytical separations. The latter includes molecular
imprinting, affinity chromatography and biospecific analyte
detection.
[Back to top]
A Review of Process Analytical Technology (PAT)
in the U.S. Pharmaceutical Industry
James Munson, C. Freeman Stanfield and Bir Gujral
Process Analytical Technologies (PAT) are used to provide
timely analysis of critical quality parameters with the end
goal of improving final product quality as well as reducing
manufacturing costs, thereby significantly benefiting the
Pharmaceutical Industry. PAT involves mostly on-line or in-line
testing, which can be an invasive or non-invasive process
that analyzes the sample while it is part of the process stream.
There is no sample preparation in the testing, thus saving
time and avoiding possible errors in sample preparations.
PAT uses vendor specifications based on science and common
sense to exhibit, ‘fit for purpose’ rather than
conventional USP paradigm, ‘one specification fits all,’
which is based upon documentation but lacking in scientific
logic. The current FDA guidance is to adapt its traditional
regulatory scrutiny to PAT advancement. The Pharmaceutical
Industry is using innovative PAT methods to improve the logical
basis for establishing regulatory specifications, promoting
continuous improvement and improving manufacturing. Multivariate
tools are used in PAT for design, data acquisition and analysis.
These tools are used in conjunction with statistical design
of experiments, response surface methodologies, and process
simulation and pattern recognition under the control of various
knowledge management systems. For example, NIR Spectroscopy
is used in drug product production at almost each step of
tablet manufacturing from raw materials control to content
uniformity analysis of the dosage unit. The spectral data
set is usually multivariate in nature. This is due not only
to the different ranges and peaks in a spectrum, which are
influenced by the nature of the product but also due to several
interlinked factors that influence the appearance of the spectrum.
When NIR is used in PAT, the materials are blended to uniformity
rather than a fixed time. This type of advance control gives
better batch-to-batch consistency and better product quality,
which eliminate reworks/rejects, and there are no Out Of Specification
(OOS) reports to file under PAT. The product is “engineered
for Quality”, as opposed to “tested to Quality”.
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