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

  • Harald JohnEmail author


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.


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.



5-Hydroxytryptamine (serotonin) receptor










Atmospheric pressure chemical ionization


Active pharmaceutical ingredient






Blood–brain barrier










Collision-induced dissociation




Central nervous system




Chronic obstructive pulmonary disease




Double focusing sector field mass spectrometer




Electrospray ionization




Formic acid


Fast atom bombardment


Gastrointestinal tract


Glucuronide conjugate




Heptanesulfonic acid


High-performance liquid chromatography




Irritable bowel syndrome






Ion trap

lin range

Linear range


Liquid–liquid extraction

log P

Logarithm of octanol/water partition coefficient




Methyl-tert butyl ether




Multiple reaction monitoring


Full scan mass spectrometry


Tandem mass spectrometry, product ion scan


Mono-isotopic molecular weight


Not specified




Organophosphorus compound


Triple quadrupole mass spectrometer


Quaternary tropane alkaloid








Selected ion monitoring


HPLC solvent


Solid-phase extraction


Single quadrupole mass spectrometer




Tropane alkaloid










Tertiary tropane alkaloids


World Health Organisation




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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