Biomedical Engineering Reference
In-Depth Information
We refer to LC-MS/MS methods that were used to investigate diffusion through
bronchial tissue in vitro [
74
] and for toxicological screening [
54
] . In addition, the
misuse of ipratropium in equine sports was investigated by LC-MS [
24
] .
Littorine
(Lit; C
17
H
23
NO
3
; MW 289.17 g/mol; CAS-No. 21956-47-8; 8-methyl-8-
azabicyclo[3.2.1]octane-3-yl) (2R)-2-hydroxy-3-phenylpropanoate).
Littorine is the natural plant precursor for biosynthesis of
S
-hyoscyamine repre-
senting its isobaric isomer (Fig.
1
). Even though littorine exhibits high affinity to
MR similar to hyoscyamine [
35
] it is not used as drug, most reasonably due to its
low concentration in plants.
A LC-ESI MS/MS method is referred for analysis of in vitro stability in human
and rabbit serum [
50
] .
N
-methyl scopolamine (MeS; methscopolamine; C
18
H
24
NO
4
; MW 318.17 g/mol;
CAS-No; 13265-10-6; (1R,2R,4S,7S)-7-{[(2S)-3-hydroxy-2-phenylpropanol]oxy}-
9,9-dimethyl-3-oxa-9-azoniatricyclo[3.3.1.0
2,4
]nonane).
Methylscopolamine is a QTA obtained by N-methylation of scopolamine (Fig.
1
).
It exhibits non-selective antimuscarinic activity and is used as adjunctive therapy
for the treatment of peptic ulcer, to treat nausea and vomiting due to motion sickness
and for the management of irritable bowel syndrome [
75
]. The tritiated form of
methylscopolamine is often used in in vitro MR binding assays to investigate recep-
tor affinity and competition by other agents [
76
] .
Here we refer to a study on TA CNS penetration analysed by LC-ESI MS/MS [
77
] .
N
-butyl scopolamine (BuS; C
21
H
30
NO
4
; MW 360.22 g/mol; CAS.-No; 149-64-4;
[7(S)-(1a ,2 b ,4 b ,5 a ,7 b )]-9-butyl-7-(3-hydroxy-1-oxo-2-phenylpropoxy)-9-methyl-
3-oxa-9-azonitricyclo[3.3.1.0
2,4
]nonane).
N
-butyl-scopolamine is a QTA representing the N-butylated derivative of scopol-
amine (Fig.
1
).
N
-butyl-scopolamine acts as an anticholinergic and since mid 1950s
is widely used as antispasmodic inducing smooth-muscle relaxing to treat acute
colics, abdominal pain and cramps.
N
-butyl-scopolamine also binds to nicotinic
receptors thus inducing ganglion-blocking [
30,
32
] .
We refer to LC-MS techniques that were used to investigate hydrolytic stability
in plasma [
50
], prove drug abuse in horses [
78
], and analyse PK behaviour in man
[
79
] .
Tiotropium
(Tio; C
19
H
22
NO
4
S
2
; MW 392.10 g/mol; CAS-No; 186691-13-4;
(1a ,2 b ,4 b ,7 b )-7-[(hydroxydi-2-thienylacetyl)oxy]-9,9-dimethyl-3-oxa-9-azoni-
atricyclo[3.3.1.0
2,4
]nonane).
Tiotropium is a QTA representing a synthetic ester of N-methylated scopine
(Fig.
1
). This drug is clinically used as anticholinergic long-acting bronchodilator
applied once daily as aerosolized solution to treat airway diseases such as COPD.
Tiotropium is considered as a selective inhibitor of MR subtype M1 and M3 thus
not enhancing mucus production [
31
] .
PK studies in man analysed by LC-MS and LC-MS/MS are addressed [
80,
81
] .
Tropisetron
(Trop; C
17
H
20
N
2
O
2
; MW 284.15 g/mol; CAS-No; 89565-68-4; (1R,5S)-
8-methyl-8-azabicyclo[3.2.1]octane-3-yl 1H-indole-3-carboxylate).
