Biomedical Engineering Reference
In-Depth Information
In contrast to TA introduced above, granisetron does not possess an azabicyclo-octane
moiety (tropane skeleton) but instead an azabicyclo-nonane system representing a
methylene-extended bicyclic compound (Fig.
1
). Nevertheless, similarities of chem-
ical structure and pharmacological activity justify its integration into the group of
TA. Similar to bemesetron, granisetron acts as a selective serotonin antagonist on
5-HT
3
receptors. It is clinically used as daily antiemetic especially administered
orally or intravenously to treat post-operative as well as chemotherapy-associated
vomiting and nausea [
70,
71
] .
We address LC-MS/MS procedures for granisetron that were applied for PK
studies in rats [
72
] and man [
71,
73
] .
Homatropine
(Hatr; C
16
H
21
NO
3
; MW 275.15 g/mol; CAS-No; 87-00-3; 8-methyl-8-
azabicyclo[3.2.1]octane-3-yl 2-hydroxy-2-phenylacetate).
Homatropine is a synthetic parasympatholytic representing the ester of tropine and
mandelic acid (Fig.
1
). This drug antagonizes acetylcholine on MR and is thus used as
mydriatic with less detrimental paralytic effects on ciliary eye muscle than atropine but
showing faster and shorter action [
1,
33
]. Therefore, it belongs to the WHO list of essen-
tial medicines as mydriatic eye drops representing an alternative to atropine [
41
] .
We refer to a LC-ESI MS/MS method applied to characterize hydrolytic stability
of homatropine in plasma [
50
] .
Hyoscyamine
(Hyo; C
17
H
23
NO
3
; MW 289.17 g/mol; CAS-No; 101-31-5; (8-methyl-
8-azabicyclo[3.2.1]octane-3-yl) 3-hydroxy-2-phenylpropanoate).
Hyoscyamine is the natural TTA (
S
-hyoscyamine) isolated from plants of the
solanaceae
family, that represents the lead structure for all other TA-derived drugs
(Fig.
1
). Despite its chemical polarity hyoscyamine exhibits strong lipophilic prop-
erties (especially under basic, non-protonating conditions) that enable rapid and
nearly complete absorption in the GIT and passage of the blood-cerebrospinal fluid
barrier. This alkaloid acts as competitive non-selective antagonist of acetylcholine
on MR. Hyoscyamine is given orally or sublingually to relief visceral spasm of the
GIT as well as spasm of the biliary and genito-urinary tract. If administered as pure
S
-hyoscyamine (eutomer) the drug has twice the potency of racemic atropine [
33
] .
LC-MS approaches were introduced to investigate biotransformation in vitro
[
49,
50
] and PK behaviour in man [
48,
49
] .
Besides scopolamine,
S
-hyoscyamine represents the most toxic TA in
Datura
plants causing severe to fatal intoxications. Evidence of
Datura
intoxication was
enabled by LC-MS procedures presented in this chapter [
11-
15,
53,
55,
57
] .
Ipratropium
(Ipra; C
20
H
30
NO
3
; MW 332.22 g/mol; CAS-No. 60205-81-4; [8-methyl-
8-(1-methylethyl)-8-azoniabicyclo[3.2.1]
octane-3-yl]
3-hydroxy-2-phenyl-
propanoate).
Ipratropium is a QTA produced by N-alkylation (iso-propyl) of hyoscyamine
(Fig.
1
). When inhaled as aerosolized agent it is a short-acting (3-6 h) antimusca-
rinic especially on MR subtypes M1-3 present in the lung. Therefore, it is clinically
used as bronchodilator, antiasthmatic and drug for chronic obstructive pulmonary
disease (COPD) [
31,
33
]. Ipratropium is part of the WHO list of essential medi-
cines [
41
] .
