Handbook of Pharmaceutical Analysis (Drugs and the Pharmaceutical Sciences: a Series of Textbooks and Monographs)

599 Pages·2002·5.05 MB·English

by  Lena Ohannesian

ISBN: 0-8247-0462-2
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Preface
TwentyyearshavepassedsincethepublicationofthefirstvolumeofPharmaceu-
tical Analysis, which has since evolved into the Handbook of Pharmaceutical
Analysis. The original two volumes succeeded in concisely filling the gap be-
tweenundergraduatetextanddetailedmonographonpharmaceuticalanalysisfor
practitioners of the pharmaceutical sciences. As with other branches of science,
the technologies employed in pharmaceutical analysis today have advanced tre-
mendouslyoverthelasttwodecades,withmethodologiesbecomingroutinethat
were purely experimental a few years ago.
Our goals in preparing this revised version were to bring the text up to
datewiththemostimportantdevelopmentsinthefieldofpharmaceuticalanalysis
while still preservingthe scope and levelof coverage of our previoustexts. We
have tried to maintain the intermediate level of coverage throughout the book,
witheachchaptercontainingdetaileddescriptionsoftheory,instrumentation,and
applications,aswellaspertinentreferences.Wedecidedtocombinethechapters
into a single volume for convenience and thus it is being published as a single,
authoritativehandbook.Thisbookisnotintendedtobeacomprehensiveresource
initself,buttogivethereaderbackgroundinformationonthemostwidelyused
techniquesand,withalmost2000references,todirectthereadertomoredetailed
sources in the scientific literature.
WehaveincludedmanyofthechaptersfromPharmaceuticalAnalysis,in
updated form, since they continue to provide the backbone of pharmaceutical
analysisforthebook.However,becauseoftheirlimitedapplications inmodern
pharmaceutical analysis, we have elected not to include some chapters such as
v
vi Preface
thoseonthin-layerchromatography,pyrolysis-gaschromatography,gaschroma-
tography, and functional group analysis.
Before you can perform any of the analytical techniques described in this
book, it is first necessary to obtain your drug substance. It is becoming clearer
thatmanydrugscanexistindifferentpolymorphicforms,whichcanbehavevery
differentlyfromoneanotherduringformulationandafteradministration.Chapter
1addressesthistopic.Chapter2dealswiththetechniquesthatareoftennecessary
forseparatingthedrugfromtheothercomponentsofapharmaceuticalformula-
tionorbiologicalsampleand/orpreparingthedrugsampleforoneoftheanalyti-
cal methods that are covered in later chapters. This chapter also introduces the
reader to the concept of validation for assays of drugs in plasma, which, since
the results of these measurements are critical in determining the safety margins
for exposure in humans versus animals in toxicity studies, is subject to close
scrutiny by regulatory authorities during the approval of new drugs. The sound
scientificprinciplesthatunderlietheFDAguidancesinthisareahave,byapro-
cess of osmosis, influenced government and academia as well.
FollowingChapter3onhigh-performanceliquidchromatography,wehave
included a chapter on the many new applications of mass spectrometry. This
technique,usuallyincombinationwithhigh-performanceliquidchromatography,
has become themainstay of metabolite ordecomposition product identification,
and its great potential for selectivity and sensitivity has proven invaluable for
manydrugandmetaboliteassays.Thevarioustechniquesappliedtohigh-perfor-
mance liquid chromatography for removing the chromatographic solvents and
introducingthesolutesdirectlyintothemassspectrometer,withouttheneedfor
extraction,derivatizationorheating,makehigh-performanceliquidchromatogra-
phy coupled with mass spectrometry especially valuable for peptides and heat
labile molecules.
Chapter5coversultraviolet–visiblespectroscopyandChapter6,onimmu-
noassay techniques, emphasizes the wide array of new methodologies that do
not use radioisotopes. Chapter 7 discussesone of the most novel techniques for
chromatographic separation of molecules—capillary electrophoresis—and its
widespreadapplicationstopharmaceuticals.Chapter8,‘‘AtomicSpectroscopy,’’
and Chapter 9, ‘‘Luminescence Spectroscopy,’’ contain current information on
these important technologies.
Chapter10,onnuclearmagneticresonancespectroscopywasincludedbe-
causeoftheuniquerolethatnuclearmagneticresonancespectroscopyhasinthe
study ofpolymorphisms as well asin verification of compoundidentity and the
structuralconfirmationofmetabolicordecompositionproductsofdrugs.Chapter
11, ‘‘VibrationalSpectroscopy,’’ reflects the invaluablecontributions that those
techniques such as infrared spectroscopy have made to the analysis of formula-
tions, among other studies.
Preface vii
Finally,wecouldnotignoreanotherareainwhichtheregulatoryauthorities
havehadamajorimpactonpharmaceuticalanalysisinthepharmaceuticalindus-
try.Ourconcludingchapterdealswithprocessvalidationasitappliestopharma-
ceutical analysis.
Lena Ohannesian
Anthony J. Streeter

Contents
Preface v
Contributors xi
1. Form Selection of Pharmaceutical Compounds 1
Ann W. Newman and G. Patrick Stahly
2. Preparation of Drug Samples for Analysis 59
David E. Nadig
3. High-Performance Liquid Chromatography 87
Thomas H. Stout and John G. Dorsey
4. Mass Spectroscopy in Pharmaceutical Analysis 151
Frank J. Belas and Ian A. Blair
5. Ultraviolet–Visible Spectroscopy 187
John H. Miyawa and Stephen G. Schulman
6. Immunoassay Techniques 225
Jean W. Lee and Wayne A. Colburn
ix