| It is 17 years since the publication of the 2nd edition of ‘Clarke’,
as this book is known by the analytical profession. Considering the number
of new drugs legitimately introduced since that time and recognising
that analytical methodology improves its sensitivity by a factor of 1,000
every 10 years, it is not difficult to justify the publication of this
latest edition.
For those acquainted with previous editions, the new work has a familiar
feel. The large amount of extra material, however, means it can no longer
be contained in a single handy volume. The new edition is literally two
distinct books. Volume 1 has 18 chapters on general topics, usually environments
in which an analyst might work, and a further 13 chapters on specific
analytical techniques. Volume 2, the bulk of the work, contains the familiar
monographs and some usefully indexed data.
Although the first volume may be considered a textbook to be read at
leisure or for general education, it still contains much factual information
that does not necessarily appear in the monographs in volume 2. For example,
the chapters on drugs in hospital toxicology and therapeutic drug monitoring
contain extensive lists of therapeutic and toxic plasma levels for drugs.
The chapters in volume 1 are written by authors of international repute
and may safely be taken as authoritative statements of current practices
and state of the art. My reservations relate to how the message is put
across. The chapter on thin-layer chromatography, for example, is written
without a diagram or picture of the physical operation involved in this
form of chromatography. Would a description without such an illustration
make any sense to someone who does not know what the technique does?
The desirable goal of covering each subject area in reasonable depth
may occasionally result in overlapping material. However the chapters
are not written in isolation and considerable work has evidently gone
into integrating some aspects. The chapters on chromatography list standard
systems for thin-layer chromatography, high performance liquid chromatography
and gas chromotography and these are mostly the systems used in the monographs.
The chapter on drugs in sport is particularly relevant at the moment,
with an Olympic year coming up, although I would rather have seen the
treatment of racehorses and humans kept as separate discussions. Reading
the popular press on drugs in sport would lead to the simplistic idea
that a named drug is either present or not present in the test sample.
It is particularly illuminating to discover that the testing rules are
no more specific and that “the finding of a prohibitive substance
means the finding of the substance itself or a metabolite of the substance”.
Further, the definition of the presence of high levels of testosterone
in male athletes depends not on the detection of the substance itself,
but on the ratio of the substance to luteinising hormone in the same
subject. It would have been useful to expand on these important points.
Most of the chapters on methodology have been completely rewritten or
cover new subjects. Although chromatography was the mainstay of quantitative
drug analysis in the latter half of the 20th century, in more recent
years, analysts have explored every available technique and this is illustrated
by the chapters on nuclear magnetic resonance, near infrared spectroscopy
and, as discussed in a chapter on emerging techniques, acoustic spectroscopy
and lab-on-a-chip developments. Neither the chapter on mass spectrometry
nor the one on high performance liquid chromatography, however, do full
justice to the importance of HPLC-GC in modern bioanalysis.
The second volume contains over 1,300 updated monographs and 400 new
ones; no compounds appearing in the second edition appear to have suffered
the fate of nearly 200 that were dropped from the first edition, although
the older analyst should be warned that “amphetamine” now
appears as “amfetamine”. Almost all monographs now include
ultraviolet, infrared and mass spectra. Despite the wealth of detail
on new techniques in volume 1, few of these techniques and approaches
have found their way into the monographs. Perhaps this is because the
general philosophy of the work is geared towards screening or identification
rather than quantification. Thus, methods of analysis in plasma, when
mentioned, describe mainly traditional HPLC or GC methods.
There is a chapter on pharmacokinetics and drug metabolism in volume
1, which rightly stresses the importance of understanding these facets
of drug behaviour when interpreting the results of analyses. It was disappointing
therefore that more information was not available in the monographs.
Even where a section on disposition does appear in the monograph it is
often brief, although with the importance placed on metabolism and pharmacokinetics
in the registration process for new drugs it is unlikely that detailed
information is missing from the scientific literature. Where statements
on disposition are given, no reference is included, which seems a surprising
omission.
Volume 2 concludes with a hefty section (Part 3) on drug data containing
indexes of analytical data, most of which presumably already appears
in the monographs and the chapters on techniques. Much of this is probably
more easily retrieved from an electronic version of the product, but
it is useful to have it indexed in this hard-copy version. These listings
also emphasise the enormous amount of careful practical work that must
have gone into compiling the data.
Because of its comprehensive all-purpose coverage the monographs need
careful reading. For example TLC analyses may list the chemical entity
that occurs in a dosage form (for example, nandrolone esters), whereas
the bioanalyst more usually is looking for the free, active entity.
I did not set out to discover any typographical errors (the prerogative
of the book reviewer throughout the ages), mainly because I did not expect
to see any, but I could not help wondering what the “pared serum
and saliva samples” were in the chapter on drugs and saliva. And
the unfortunate subject who died three days after committing suicide
intrigued me too.
The new edition has been four years in preparation and has been eagerly
awaited. Despite the wide subject matter, its value to the specialist
is not diluted and I have no doubt it will find a prominent, and deserved,
place in all laboratories involved in aspects of drug analysis.
Joseph Chamberlain
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