Biomedical Engineering Reference
In-Depth Information
a1-AR blocking properties. In China it is used for therapy of, e.g. circulatory disor-
ders, gastrointestinal colic, nephritis, hepatitis and eclampsia but primarily against
septic shock and severe acute respiratory syndrome (SARS). Anisodamine is less
toxic than atropine and of less CNS toxicity than scopolamine [
6,
38
] .
Biotransformation of anisodamine in an in vivo rat model as well as in liver
homogenates was analysed by LC-ESI MS/MS and is referred later on [
6
] .
Anisodine
(Adi; C
17
H
21
NO
5
; MW 319.14 g/mol; CAS-No. 52646-92-1;
9-methyl-3-oxa-9-azatricyclo[3.2.1.0
2,4
]nonane-7-yl
a -hydroxy- a -hydroxy-
methyl-benzeneacetate).
Anisodine is a natural TTA that represents a derivative of the scopolamine structure
mono-hydroxylated at the tropic acid moiety (Fig.
1
). Similar to anisodamine it was
extracted from Chinese herb
Anisodus tanguticus
(Maxim.) Pascher and also exhibits
a1-AR blocking properties and non-specific anticholinergic effects. Accordingly, in
China anisodine is used for the therapy of the same indications as described for aniso-
damine, most often to treat transmissible shock. Toxicity and side effects of anisodine
are smaller than those for atropine, scopolamine and anisodamine [
5
] .
This topic chapter refers to rat in vivo biotransformation studies performed by
LC-ESI MS/MS [
5,
40
] .
Atropine
(Atr; C
17
H
23
NO
3
; MW 289.17 g/mol; CAS-No. 51-55-8; 8-methyl-8-
azabicyclo[3.2.1]octane'-3-yl 3-hydroxy-2-phenylpropanoate).
This TTA is an injectable core medicine listed in the World Health Organization's
(WHO) “Model list of essential medicines” [
41
] . Atropine (Fig.
1
) acts as a com-
petitive MR antagonists used clinically as, e.g. parasympatholytic for pre-anaesthe-
sia medication, ophthalmologic procedures and as antidote for the therapy of
anticholinesterase poisoning [
42,
43
]. A corresponding PK study in man monitoring
atropine as antidote by LC-MS/MS is referred in this chapter [
44
] .
Atropine is the racemic mixture of
R
- and
S
-hyoscyamine produced during the
pharmaceutical plant extraction process.
R
-hyoscyamine is nearly inactive on MR
(distomer) whereas S-hyoscyamine exhibits high affinity (eutomer). Nevertheless,
due to economic reasons atropine is typically administered even though only half of
the applied dose (
S
-hyoscyamine) is pharmacologically active on MR. Surprisingly,
there is still little information about different pharmacokinetic behaviour of both
enantiomers anyhow [
46,
47
] .
LC-MS-based procedures for chiral and enantioselective analysis of mammalian
samples are discussed in the Sects.
3.2
and
3.2.2
[
47-
50
]. Detailed data on biotrans-
formation in vivo especially in man are quite rare. LC-ESI MS/MS procedures are
referred that allowed metabolite identification in animals in in vivo and in vitro
models [
51,
52
] .
Intoxications with higher concentrations will cause tachycardia, mydriasis, CNS
excitations and hallucinations, coma and ultimately death [
42
] . Incorporation of
atropine (more correctly
S
-hyoscyamine) is the predominant reason for TA intoxica-
tion after ingestion of
Datura
plants.
LC-MS methods to investigate atropine intoxications by analysis of plasma,
serum or whole blood [
11,
53,
54
] , urine [
12-
14,
55
] , hair [
56,
57
] and viscera [
15
]
are presented in this chapter.
