Biomedical Engineering Reference
In-Depth Information
Bemesetron (Beme; MDL 72,222; C 15 H 17 NO 2 Cl 2 ; MW 313.06 g/mol; CAS-No; 40796-
97-2; [(1S,5R)-8-methyl-8-azabicyclo[3.2.1]octane-3-yl] 3,5-dichlorobenzoate).
Bemesetron is a synthetic ester of tropine and dichlorobenzoylic acid (Fig. 1 ). In
contrast to TA introduced above, bemesetron primarily acts as a selective serotonin
antagonist on the 5-HT 3 R in the CNS and GIT. Therefore, it was tested as an inject-
able antiemetic drug for cancer chemotherapy to treat vomiting and nausea but is
not in clinical use [ 36, 37, 58 ] .
Biotransformation products present in urine were identified by LC-APCI MS [ 37 ] .
Benztropine (Benz; benzatropine; C 21 H 25 NO; MW 307.19 g/mol; CAS-No; 86-13-5;
(3-endo)-3-(diphenylmethoxy)-8-methyl-8-azabicyclo[3.2.1]octane).
Benztropine is a synthetic tropine derivative (Fig. 1 ) that acts as anticholinergic
agent with similar pharmacological properties as atropine but exhibiting much
stronger antihistamine and dopamine reuptake inhibitor activity. It is clinically used
as an orally administered second-line drug to treat Parkinson's disease improving
tremor and rigidity [ 59, 60 ] .
Studies on in vivo biotransformation of benztropine in rats were supported by
LC-ESI MS analysis and are referred herein [ 59 ] .
Cimetropium (Cim; C 21 H 28 NO 4 ; MW 358.20 g/mol; CAS-No. 51598-60-8; 9-cyclo-
propylmethyl-7-(3-hydroxy-2-phenyl-propionyloxy)-9-methyl-3-oxa-9-azonia-tri-
cyclo [3.3.1.0 2,4 ]nonane).
Cimetropium is a QTA representing an N-alkylated derivative of scopolamine
(Fig. 1 ). It exhibits antispasmodic activity on smooth muscle cells in the GIT.
Therefore, it is clinically used for oral long-term treatment of irritable bowel syn-
drome with minimal effects on vascular receptors [ 32, 61 ] .
We refer to LC-MS-based methods for a PK study [ 61 ] as well as in vitro
biotransformation studies with liver microsomes [ 23, 62 ] .
Cocaine (Coc, benzoylmethylecgonine, C 17 H 21 NO 4 ; MW 303.15 g/mol; CAS-No.
50-36-2; methyl (1R,2R,3S,5S)-3-(benzoyloxy)-8-methyl-8-azabicyclo[3.2.1]octane-2-
carboxylate).
In contrast to other TA, cocaine derives from Erythroxylaceae coca and may be
considered as a derivatized tropine structure (Fig. 1 ). Cocaine is a serotonin-norepi-
nephrine-dopamine reuptake inhibitor that stimulates CNS, suppresses appetite and
may be applied as topical local anaesthetic being notorious for causing devastating
addiction [ 1 ]. Furthermore, cocaine induces euphoria, decreased fatigue together
with alterations in pulse and respiration. Due to the completely different pharmacol-
ogy of cocaine when compared to other TA and the huge number of scientific pub-
lications on LC-MS analysis of cocaine in biological fluids, cocaine will not be
considered in this summary. Instead we like to refer the reader to excellent reviews
on this topic providing relevant and complementary information [ 63- 69 ] .
Granisetron (Gran; C 18 H 24 N 4 O; MW 312.19 g/mol; CAS-No. 109889-09-0; endo-1-
methyl- N -[9-methyl-9-azabicyclo-[3,3,1]nonane-3-yl]-1H-imidazole-3-
carboxamide).
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