| Application of 1-alkylamines to a liquid chromatographic/turbo ionspray tandem mass spectrometric method for quantifying metabolites of a new bone anabolic agent, TAK-778, in human serum. | |
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MedLine Citation:
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PMID: 12112746 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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We investigated the application of alkylamines, as additives to the mobile phase, to a quantification method for the metabolites, M-III and M-IV, of TAK-778, which is a new bone anabolic agent, in human serum using liquid chromatography/tandem mass spectrometry (LC/MS/MS). Prior to setting up the analytical method, we found that 1-alkylamines co-existing with M-III and M-IV in the turbo ionsprayed solution formed 1-alkylammonium adduct molecules of these metabolites during the ionization process, and the abundance of the adduct ions was considerably higher than that of protonated molecules ([M + H](+)s) of these metabolites. Based on these findings, we investigated a variety of 1-alkylamines and their spiked concentrations in the mobile phase for LC/MS/MS analysis to obtain higher sensitivities for the quantification of these metabolites. After these examinations, we found that 1-hexylamine at a final concentration of 0.05 mmol l(-1) was the most suitable additive for the mobile phase, and set the selected reaction monitoring (SRM) ions for the 1-hexylammonium adduct molecule and [M + H](+), allowing about a fivefold gain in the SRM chromatographic peak compared with that without 1-hexylamine. The adduct ion was considered to be formed by interaction between the amino group of 1-hexylamine and the phosphoryl group of M-III and M-IV. The internal standard (I.S.) used was deuterated M-III for each metabolite. The analytes and I.S. were extracted with diethyl ether from serum samples at neutral pH and injected into the LC/MS/MS system with a turbo ionspray interface. The limit of quantification for both analytes was 0.5 ng ml(-1) when 0.1 ml of serum was used, and the calibration curves were linear in the range 0.5-100 ng ml(-1). The method was precise; the intra- and inter-day precisions of the method were not more than 5.6%. The accuracy of the method was good, with deviations between added and calculated concentrations of M-III and M-IV being typically within 16.6%. This method provided reliable pharmacokinetic data for M-III and M-IV after the intramuscular administration of TAK-778 sustained-release formulation in humans. |
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Authors:
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Koichiro Teshima; Takahiro Kondo; Chie Maeda; Tsuneo Oda; Toshiaki Hagimoto; Ryoichi Tsukuda; Yoshinobu Yoshimura |
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Publication Detail:
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Type: Journal Article; Validation Studies |
Journal Detail:
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Title: Journal of mass spectrometry : JMS Volume: 37 ISSN: 1076-5174 ISO Abbreviation: J Mass Spectrom Publication Date: 2002 Jun |
Date Detail:
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Created Date: 2002-07-11 Completed Date: 2002-08-19 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 9504818 Medline TA: J Mass Spectrom Country: England |
Other Details:
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Languages: eng Pagination: 631-8 Citation Subset: IM |
Copyright Information:
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Copyright 2002 John Wiley & Sons, Ltd. |
Affiliation:
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Drug Analysis and Pharmacokinetics Research Laboratories, Pharmaceutical Research Division, Takeda Chemical Industries Ltd., 2-17-85 Juso-Honmachi, Yodogawa-ku, Osaka 532-8686, Japan. teshima_kouichirou@takeda.co.jp |
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| MeSH Terms | |
Descriptor/Qualifier:
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Alkylation Amines / chemistry* Benzothiepins / administration & dosage, blood, pharmacokinetics* Biotransformation Blood Chemical Analysis / instrumentation, methods Calibration Chromatography, High Pressure Liquid / methods* Humans Hydrogen-Ion Concentration Injections, Intramuscular Mass Spectrometry / methods* Reference Standards Sensitivity and Specificity |
| Chemical | |
Reg. No./Substance:
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0/Amines; 0/Benzothiepins; 0/TAK 778 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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