Article ; Online: Determination of tissue distribution of potent antitumor agent ureidomustin (BO-1055) by HPLC and its pharmacokinetic application in rats.
Journal of chromatography. B, Analytical technologies in the biomedical and life sciences
2013 Volume 917-918, Page(s) 62–70
Abstract: Ureidomustin hydrochloride (BO-1055) was designed as a water-soluble nitrogen-mustard, which exhibited potent anticancer activity and was selected as a candidate for preclinical studies. However, up to date, there is rarely an easy and economic method to ...
| Abstract | Ureidomustin hydrochloride (BO-1055) was designed as a water-soluble nitrogen-mustard, which exhibited potent anticancer activity and was selected as a candidate for preclinical studies. However, up to date, there is rarely an easy and economic method to quantize ureidomustin in the biological samples. The aim of this study is to develop a simple yet valid quantization method to tackle this challenge. Here we present a combined high-performance liquid chromatography with photodiode array (HPLC-PDA) method in quantizing the ureidomustin in the plasma and various organs of Sprague-Dawley rats. The method was validated in terms of precision, accuracy, and extraction recovery. Furthermore, the established method was applied to study pharmacokinetics of ureidomustin in the rat's plasma and verified via a liquid chromatography tandem mass spectrometry (LC-MS/MS) method. Calibration curves of the plasma and organ samples were falling at the range between 0.5-50μg/mL and 0.1-50μg/mL (r(2)≥0.999 and CV≤±15%), respectively. The limits of detection (LOD) were 0.1μg/mL for plasma samples and 0.05μg/mL for organ samples, while the detection limits of quantification (LOQ) were 0.5μg/mL for plasma samples and 0.1μg/mL for organ samples. The average recovery of ureidomustin was about 83%. These results demonstrated a linear pharmacokinetic pattern at dosages of 10 and 30mg/kg. The pharmacokinetic data revealed that ureidomustin was best fitted to a two-compartment model with a rapid distribution phase and a slow elimination phase. Besides, after a short intravenous administration time at the dose of 10mg/kg, ureidomustin was found to be quickly distributed to all organs in rats, accumulated mainly in the kidney, and only a limited amount was detected in the brain. |
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| MeSH term(s) | Animals ; Antineoplastic Agents/blood ; Antineoplastic Agents/chemistry ; Antineoplastic Agents/pharmacokinetics ; Chromatography, High Pressure Liquid/methods ; Limit of Detection ; Male ; Nitrogen Mustard Compounds/blood ; Nitrogen Mustard Compounds/chemistry ; Nitrogen Mustard Compounds/pharmacokinetics ; Phenylurea Compounds/blood ; Phenylurea Compounds/chemistry ; Phenylurea Compounds/pharmacokinetics ; Rats ; Rats, Sprague-Dawley ; Reproducibility of Results ; Tandem Mass Spectrometry/methods ; Tissue Distribution |
| Chemical Substances | 1-(3-((2-(dimethylamino)ethyl)carbamoyl)phenyl)-3-(4-(bis(2-chloroethyl)amino)phenyl)urea ; Antineoplastic Agents ; Nitrogen Mustard Compounds ; Phenylurea Compounds |
| Language | English |
| Publishing date | 2013-02-15 |
| Publishing country | Netherlands |
| Document type | Journal Article ; Research Support, Non-U.S. Gov't |
| ZDB-ID | 1180823-8 |
| ISSN | 1873-376X ; 0378-4347 ; 1570-0232 ; 1387-2273 |
| ISSN (online) | 1873-376X |
| ISSN | 0378-4347 ; 1570-0232 ; 1387-2273 |
| DOI | 10.1016/j.jchromb.2012.12.025 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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