Biomedical Engineering Reference
In-Depth Information
Tropisetron is a synthetic TTA containing an esterified tropine moiety (Fig.
1
).
This drug is a potent antiemetic selective 5-HT
3
receptor antagonist to treat post-
operative and chemotherapy-induced vomiting and nausea by daily intravenous or
oral administration [
70
]. Furthermore, tropisetron is a potent and selective partial
agonist of a
7
-nAChR [
39
] .
We herein refer to an in vitro biotransformation study in human liver microsomes
[
82
] and a PK study in man [
83
] both analysed by LC-MS-based methods.
Trospium
(Tros; C
25
H
30
NO
3
; MW 392.22 g/mol; CAS-No. 10405-02-4; spiro[8-
azoniabicyclo-[3,2,1]octane-8,1¢ -pyrrolidinium]-3-(hydroxydiphenyl-acetyl)-oxy).
Trospium is a QTA in which the tropine N-atom is part of two alkyl ring structures
(Fig.
1
). This drug acts as an antimuscarinic agent that is clinically used as orally
administered first-line urinary antispasmodic to treat overactive bladder (OAB) [
34
] .
Due to the absence of significant biotransformation, trospium is excreted mainly
unchanged into urine allowing to exhibit primarily local activity [
84
] .
We introduce a PK study in man [
84
] and an in vivo distribution study in rat to
elucidate CNS penetration of trospium [
77
] both analysed by LC-MS/MS.
Satropane
(Sat; C
17
H
20
NO
5
S; MW 535.13 g/mol; [6b -acetoxy-8-methyl-8-azabicy-
clo[3.2.1]octane-3-yl] paramethyl-benzenesulfonate).
Satropane is a synthetic derivative of tropine (Fig.
1
). The structure represents an
analogue of baogongteng, a TTA isolated from Chinese herb
Erycibe obtusifolia
Benth
[
4
]. In contrast to other TA, (−)-satropane exhibits agonistic activity on MR.
Due to activation of iris MR subtype M3 present in the iris-ciliary body, hyperten-
sive intraocular pressure (IOP) is reduced. Therefore, (−)-satropane is considered as
future drug to treat high IOP and glaucoma, caused by, e.g. degeneration of optic
nerve axons [
4,
85
] .
A LC-ESI MS/MS method to study distribution of satropane in rabbit is referred [
85
] .
Scopolamine
(Scp; hyoscine; C
17
H
21
NO
4
; MW 303.14 g/mol; CAS-No; 51-34-3;
(-)-(S)-3-hydroxy-2-phenylpropionic acid (1R,2R,4S,7S,9S)-9-methyl-3-oxa-9-
azatricyclo [3.3.1.0
2,4
] non-7-yl ester).
S
-scopolamine is a natural TTA biosynthesised from hyoscyamine present in
plants of the
solanaceae
family (Fig.
1
). Scopolamine acts as a non-selective anti-
muscarinic drug but exhibits sedative depressant effects on the CNS. Typically it is
applied to prevent and control motion sickness and visceral spasm but also as mydri-
atic, cycloplegic and antiemetic [
29
]. Scopolamine, similar to atropine, inhibits
secretions in the respiratory tract, stomach and of saliva and may cause psychotic
reactions in higher doses [
33
]. Administration may be oral, via injection or as trans-
dermal patch. The latter variant has also been elaborated for the treatment of OP
poisoning in dogs [
86
] .
LC-MS/MS procedures to investigate biotransformation in vivo and in vitro [
7,
87
] , to monitor PK pro fi les [
88,
89
], and to screen for intoxications [
11,
13-
15,
55-
57
] are referred in this chapter.
Hints on diverse sample origins and fields of LC-MS application given above
point up a broad spectrum of sample matrices with various complexity as well as
