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Determination of denaverine and its metabolites in urine samples by liquid chromatography-tandem mass spectrometry.
J Chromatogr A. 2008 May 02; 1189(1-2):339-46.JC

Abstract

A liquid chromatography-tandem mass spectrometric (LC-MS-MS) method was developed for the determination of the neurotropic-musculotropic spasmolytic agent denaverine and five of its metabolites in urine. In a first step beta-glucuronidase was used to cleave glucuronides in the human urine. After that samples containing denaverine and its phase I metabolites were extracted and cleaned up using an automated solid phase extraction method. An external calibration was used. The analytes were measured employing the multiple reaction-monitoring mode (MRM). The linear dynamic range for denaverine and its five metabolites determination was demonstrated from lower limit of quantification (8.0 ng/ml) to at least 500 ng/ml. The presented method is suitable for pharmacokinetic or toxicokinetic studies. With the help of reference substances some additional potential metabolites could be excluded in the urine samples. To look for additional unknown metabolites the LC-MS-MS system operated on one hand in the precursor ion mode using typical product ions of denaverine and of its metabolites and on the other hand in the product ion mode using postulated protonated molecules [M+H](+). With the help of the chromatographic behaviour and typical fragment ions of the unknown metabolites it was possible to elucidate their structures. Nine until now unknown metabolites were found in the urine samples. However, without reference substances a quantification of these analytes was not possible.

Authors+Show Affiliations

Institute of Clinical Pharmacology, Medical Faculty Carl Gustav Carus, Technical University Dresden, Fiedlerstr. 27, 01307 Dresden, Germany.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

17980885

Citation

Kilian, B, et al. "Determination of Denaverine and Its Metabolites in Urine Samples By Liquid Chromatography-tandem Mass Spectrometry." Journal of Chromatography. A, vol. 1189, no. 1-2, 2008, pp. 339-46.
Kilian B, Oertel R, Kirch W. Determination of denaverine and its metabolites in urine samples by liquid chromatography-tandem mass spectrometry. J Chromatogr A. 2008;1189(1-2):339-46.
Kilian, B., Oertel, R., & Kirch, W. (2008). Determination of denaverine and its metabolites in urine samples by liquid chromatography-tandem mass spectrometry. Journal of Chromatography. A, 1189(1-2), 339-46.
Kilian B, Oertel R, Kirch W. Determination of Denaverine and Its Metabolites in Urine Samples By Liquid Chromatography-tandem Mass Spectrometry. J Chromatogr A. 2008 May 2;1189(1-2):339-46. PubMed PMID: 17980885.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Determination of denaverine and its metabolites in urine samples by liquid chromatography-tandem mass spectrometry. AU - Kilian,B, AU - Oertel,R, AU - Kirch,W, Y1 - 2007/10/11/ PY - 2007/06/29/received PY - 2007/09/21/revised PY - 2007/09/27/accepted PY - 2007/11/6/pubmed PY - 2008/7/19/medline PY - 2007/11/6/entrez SP - 339 EP - 46 JF - Journal of chromatography. A JO - J Chromatogr A VL - 1189 IS - 1-2 N2 - A liquid chromatography-tandem mass spectrometric (LC-MS-MS) method was developed for the determination of the neurotropic-musculotropic spasmolytic agent denaverine and five of its metabolites in urine. In a first step beta-glucuronidase was used to cleave glucuronides in the human urine. After that samples containing denaverine and its phase I metabolites were extracted and cleaned up using an automated solid phase extraction method. An external calibration was used. The analytes were measured employing the multiple reaction-monitoring mode (MRM). The linear dynamic range for denaverine and its five metabolites determination was demonstrated from lower limit of quantification (8.0 ng/ml) to at least 500 ng/ml. The presented method is suitable for pharmacokinetic or toxicokinetic studies. With the help of reference substances some additional potential metabolites could be excluded in the urine samples. To look for additional unknown metabolites the LC-MS-MS system operated on one hand in the precursor ion mode using typical product ions of denaverine and of its metabolites and on the other hand in the product ion mode using postulated protonated molecules [M+H](+). With the help of the chromatographic behaviour and typical fragment ions of the unknown metabolites it was possible to elucidate their structures. Nine until now unknown metabolites were found in the urine samples. However, without reference substances a quantification of these analytes was not possible. SN - 0021-9673 UR - https://www.unboundmedicine.com/medline/citation/17980885/Determination_of_denaverine_and_its_metabolites_in_urine_samples_by_liquid_chromatography_tandem_mass_spectrometry_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0021-9673(07)01729-3 DB - PRIME DP - Unbound Medicine ER -