Biomedical Engineering Reference
In-Depth Information
The first main part of this chapter opens with general aspects of chemical TA
structures and the resulting physico-chemical properties, which determine the
adequate choice of sample preparation, separation and detection techniques.
Thereafter, pharmacological and toxicological basics of TA are outlined in gen-
eral, followed by individual introduction of those TA, that are referred to in detail
in this chapter.
The second main part of this contribution is addressed to LC-MS-based analyti-
cal procedures. Initially, we discuss important methods for sample preparation.
Afterwards characteristics of chromatographic separation are presented followed by
important issues of mass spectrometric detection including type of ionization, kind
of mass analyzers and typical scan modes for MS operation.
Subsequently, different fields of LC-MS applications are presented covering (a)
PK studies, (b) investigations of in vivo and in vitro distribution, (c) biotransforma-
tion processes in living organisms and in isolated in vitro systems, and (d) toxico-
logical screening and methods to diagnose drug abuse.
At last, the concluding remarks will point out most important facts and future
perspectives.
Cocaine was not discussed in detail as numerous reviews we refer to provide
good overviews on this drug and relevant LC-MS/MS methods.
2
Tropane Alkaloids
TA belong to a class of small molecules characterized by a derivatized tropane ring
skeleton (8-methyl-8-azabicyclo[3.2.1]octane). Hydroxylated tropane (tropine) is
esterified with diverse organic acids often representing structural analogues of, e.g.
tropic, benzoic or mandelic acid (Fig.
1
). Manifold variations are found either in
natural sources or as (semi-) synthetic active pharmaceutical ingredients (API) with
individual optimized properties.
TA have been used as magic potions, recreational, shamanic and arrow poison,
knockout drops, sedatives, hallucinogens, and medicine since ancient times [
1-
3
] .
TA are accessible from plants especially of the
solanaceae
family including
Atropa
belladonna
(deadly nightshade),
Hyoscyamus niger
(henbane),
Scopolia carniolica
(scopola),
Datura stramonium
(thornapple),
Duboisia myoporoides
(corkwood) and
Brugmansia arborea
(angel's trumpets) [
1
]. In addition, some TA (e.g. 6b -acetoxy-
2b-hydroxy-nortropane, anisodine, anisodamine, scopolamine) were identified in
herbs used in Chinese traditional medicine, e.g.
Erycibe obtusifolia
(Benth) [
4
] and
Anisodus tanguticus
(Maxim.) Pascher [
5-
7
] .
Isolation and chemical characterization of TA started in the early nineteenth cen-
tury (e.g. hyoscyamine in 1833; scopolamine in 1881; cocaine in 1862 [
1
] ) thus
representing early examples of pharmacognosy, which denominates the discovery
of drugs from medicinal plants, fungi, bacteria and marine organisms [
1,
8
] .
Today, more than 200 different natural TA are known, but only a very few are of
clinical or toxicological importance [
9
]. Most common representatives of these
