Determination of propiverine and its metabolites in rat samples by liquid chromatography–tandem mass spectrometry

Oertel, Reinhard; Kilian, B.; Siegmund, Werner; Kirch, Wilhelm

doi:10.1016/j.chroma.2006.11.021

Cited by 13 publications

(4 citation statements)

References 10 publications

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“…Propiverine ([M þ H] þ , m/z 368) also shows similar fragmentation (see Scheme 26) in addition to losses of propene and propanol at the high end (Oertel et al, 2007). Two related structures, triperiden and trihexylphenidyl, based on a common 1-phenyl-3-(piperidin-1-yl)propan-1-ol backbone show a major fragment ion due to the 1-methylidenepiperidinium ion (C 6 H 12 N þ ).…”

Section: Anticholinergic Agentsmentioning

confidence: 88%

Fragmentation of toxicologically relevant drugs in positive‐ion liquid chromatography–tandem mass spectrometry

Niessen¹

2011

Mass Spectrometry Reviews

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The identification of drugs and related compounds by LC-MS-MS is an important analytical challenge in several application areas, including clinical and forensic toxicology, doping control analysis, and environmental analysis. Although target-compound based analytical strategies are most frequently applied, at some point the information content of the MS-MS spectra becomes relevant. In this article, the positive-ion MS-MS spectra of a wide variety of drugs and related substances are discussed. Starting point was an MS-MS mass spectral library of toxicologically relevant compounds, available on the internet. The positive-ion MS-MS spectra of ∼570 compounds were interpreted by chemical and therapeutic class, thus involving a wide variety of drug compound classes, such benzodiazepines, beta-blockers, angiotensin-converting enzyme inhibitors, phenothiazines, dihydropyridine calcium channel blockers, diuretics, local anesthetics, vasodilators, as well as various subclasses of anti-diabetic, antidepressant, analgesic, and antihistaminic drugs. In addition, the scientific literature was searched for available MS-MS data of these compound classes and the interpretation thereof. The results of this elaborate study are presented in this article. For each individual compound class, the emphasis is on class-specific fragmentation, as discussing fragmentation of all individual compounds would take far too much space. The recognition of class-specific fragmentation may be quite informative in determining the compound class of a specific unknown, which may further help in the identification. In addition, knowledge on (class-specific) fragmentation may further help in the optimization of the selectivity in targeted analytical approaches of compounds of one particular class.

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Section: Anticholinergic Agentsmentioning

confidence: 88%

Fragmentation of toxicologically relevant drugs in positive‐ion liquid chromatography–tandem mass spectrometry

Niessen¹

2011

Mass Spectrometry Reviews

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“…6,7 The detection of isotopically labeled peptide pairs can be performed by liquid chromatography tandem mass spectrometry (LC-MS/MS) technology 8 and quantitative proteomic analysis is possible by multiple reaction monitoring (MRM). 9 The use of these methods enables the quantification of peptides in in vivo samples such as serum, urine and feces 10 and the identification of peptide metabolites. 11 One interesting target in the field of G protein-coupled receptor (GPCR) therapeutics is the ghrelin receptor.…”

Section: Introductionmentioning

confidence: 99%

High metabolic in vivo stability and bioavailability of a palmitoylated ghrelin receptor ligand assessed by mass spectrometry

Kostelnik

Els‐Heindl

Klöting

et al. 2015

Bioorganic & Medicinal Chemistry

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“…Propiverine and its metabolites M‐5, M‐6, and M‐23 were quantified in serum and urine using high‐performance liquid chromatography and liquid chromatography‐tandem mass spectrometry, respectively 23,24 . The analytes were extracted from serum and urine using Nexus Cartridges and Disk Cartridges SDB‐XC, respectively (Varian, Darmstadt, Germany).…”

Section: Methodsmentioning

confidence: 99%

Disposition and Antimuscarinic Effects of the Urinary Bladder Spasmolytics Propiverine: Influence of Dosage Forms and Circadian‐Time Rhythms

May

Westphal

Gießmann

et al. 2008

The Journal of Clinical Pharma

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Propiverine extended release is expected to be better tolerated compared to immediate release tablets because of slower drug release and reduced formation of active metabolites in the colon. CYP3A4 and ABCC2, the major variables in pharmacokinetics of propiverine, are less expressed in the colon. Therefore, disposition and pharmacodynamics of propiverine were measured in a double-blind, double-dummy, crossover study with administration of 15 mg immediate release 3 times daily for 7 days compared to 45 mg extended release once daily for 7 days in 24 healthy subjects. Twelve subjects also received 15 mg propiverine intravenously. Serum and urine propiverine levels were measured repeatedly following oral administration on day 7 for up to 72 hours and correlated to duodenal expression of CYP3A4, ABCB1, and ABCC2. Propiverine immediate release 3 times daily was not different to extended release once daily in areas under the serum concentration-time curve (0-24 hours) and peak-trough fluctuation. The areas under the serum concentration-time curve of propiverine immediate release was circadian-time-dependent, with the lowest values during the night. Disposition of intravenous propiverine and propiverine immediate release administered in the night was influenced by intestinal expression of ABCC2. We concluded that oral absorption of propiverine is site-dependent and influenced by dosage form and circadian-time-dependent elimination processes.

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Determination of propiverine and its metabolites in rat samples by liquid chromatography–tandem mass spectrometry

Cited by 13 publications

References 10 publications

Fragmentation of toxicologically relevant drugs in positive‐ion liquid chromatography–tandem mass spectrometry

Fragmentation of toxicologically relevant drugs in positive‐ion liquid chromatography–tandem mass spectrometry

High metabolic in vivo stability and bioavailability of a palmitoylated ghrelin receptor ligand assessed by mass spectrometry

Disposition and Antimuscarinic Effects of the Urinary Bladder Spasmolytics Propiverine: Influence of Dosage Forms and Circadian‐Time Rhythms

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