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Liquid Chromatography-Mass Spectrometric Analysis of Tropane Alkaloids in Mammalian Samples: Techniques and Applications

  • Harald JohnEmail author
Chapter

Abstract

Tropane alkaloids (TA) are bioactive small molecules containing an esterified bicyclic tropane moiety. TA represent natural plant poisons and (semi)synthetic drugs, most of them (e.g. atropine, benzatropine, N-butyl scopolamine, cimetropium, homatropine, ipratropium, N-methyl scopolamine, scopolamine, tiotropium, trospium) antagonizing acetylcholine at muscarinic receptors (MR) and some of them (e.g. bemesetron, granisetron, scopolamine, tropisetron) antagonizing serotonin at the 5-HT3 receptor (5-HT3R). Therapeutic effects on MR include mydriasis, spasmolysis of the gastrointestinal tract, overactive bladder and of the respiratory system. Due to their binding to the 5-HT3R, TA are used as antiemetic to treat vomiting and nausea. In addition, a few TA interact with α1-adrenoreceptors thus being used to improve blood flow for the treatment of septic shock (e.g. anisodamine, anisodine). Furthermore, ingestion of plants containing natural TA such as hyoscyamine and scopolamine may cause fatal intoxications.

Determination of TA is required for pharmacokinetic and distribution studies, to elucidate biotransformation in vivo and in vitro as well as to identify and quantify any poison in toxicological and forensic samples. For this purpose LC-MS-based methods are often applied. The present chapter comprehensively introduces and discusses diverse LC-MS procedures for 19 natural and synthetic TA that are of relevance as drug and poison. Individual compounds are briefly introduced providing basic pharmacological information. Their physico-chemical properties are addressed exemplifying the impact on sample preparation (e.g. precipitation, liquid–liquid extraction, solid-phase extraction) and chromatographic separation. Mass analyzers and scan modes used following electrospray and atmospheric pressure chemical ionization are commented and statistical evaluation of their frequency of use is illustrated. MS/MS-based metabolite identification strategies applied to TA analysis are pointed out. At least diverse fields of applications are categorized to review several examples of PK, distribution, and biotransformation studies as well as toxicological analysis. Concluding remarks point out potential future trends and possibilities of LC-MS in clinical pharmacology.

Keywords

Muscarinic Receptor Multiple Reaction Monitoring Atmospheric Pressure Chemical Ionization Multiple Reaction Monitoring Mode Tropane Alkaloid 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Abbreviations

5-HT3R

5-Hydroxytryptamine (serotonin) receptor

ACN

Acetonitrile

Ada

Anisodamine

Adi

Anisodine

AGP

Alpha-glycoprotein

APCI

Atmospheric pressure chemical ionization

API

Active pharmaceutical ingredient

Atr

Atropine

AtrE

Atropinesterase

BBB

Blood–brain barrier

Becg

Benzoylecgonine

Beme

Bemesetron

Benz

Benztropine

BuS

N-butyl-scopolamine

CID

Collision-induced dissociation

Cim

Cimetropium

CNS

Central nervous system

Coc

Cocaine

COPD

Chronic obstructive pulmonary disease

Da

Dalton

EBQ1Q2

Double focusing sector field mass spectrometer

EE

Ethylacetate

ESI

Electrospray ionization

Et2O

Diethylether

FA

Formic acid

FAB

Fast atom bombardment

GIT

Gastrointestinal tract

glucu

Glucuronide conjugate

Gran

Granisetron

Hep-SA

Heptanesulfonic acid

HPLC

High-performance liquid chromatography

hyo

Hyoscyamine

IBS

Irritable bowel syndrome

Ipra

Ipratropium

iso

Isocratic

IT

Ion trap

lin range

Linear range

LLE

Liquid–liquid extraction

log P

Logarithm of octanol/water partition coefficient

MeOH

Methanol

Me-O-tBu

Methyl-tert butyl ether

MeS

Methylscopolamine

MRM

Multiple reaction monitoring

MS

Full scan mass spectrometry

MS/MS

Tandem mass spectrometry, product ion scan

MW

Mono-isotopic molecular weight

n.s.

Not specified

OAc

Acetate

OP

Organophosphorus compound

QqQ

Triple quadrupole mass spectrometer

QTA

Quaternary tropane alkaloid

ref

Reference

Sat

Satropane

Scp

Scopolamine

SIM

Selected ion monitoring

Solv

HPLC solvent

SPE

Solid-phase extraction

SQ

Single quadrupole mass spectrometer

T

Temperature

TA

Tropane alkaloid

Tio

Tiotropium

Trop

Tropisetron

Tros

Trospium

TSP

Thermospray

TTA

Tertiary tropane alkaloids

WHO

World Health Organisation

α1-AR

α1-Adrenoreceptor

α7-nAChR

α7-Nicotinic receptor

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Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  1. 1.Bundeswehr Institute of Pharmacology and ToxicologyMunichGermany

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