Huber, S. and Antoni, F. and Schickaneder, C. and Schickaneder, H. and Bernhardt, G. and Buschauer, A. (2015) Stabilities of neutral and basic esters of bendamustine in plasma compared to the parent compound: Kinetic investigations by HPLC. JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS, 104. pp. 137-143. ISSN 0731-7085, 1873-264X
Full text not available from this repository. (Request a copy)Abstract
Esters of the cytostatic bendamustine (1), previously demonstrated to be much more potent than the parent compound as antiproliferative agents in vitro, were investigated for stability in buffer and plasma, as well as against porcine liver esterase in the presence of different amounts of albumin using a validated RP-HPLC method with fluorescence detection. The hydrolysis of the nitrogen mustard moiety was retarded (for 1: approximately 130 vs. 11 min) in the presence of plasma proteins. For the derivatives, both cleavage of ester and nitrogen mustard moieties were analyzed. Enzymatic hydrolysis was very fast in the case of 2-pyrrolidino-, 2-piperidino- and 2-(4-methylpiperazino)-ethyl esters, whereas methyl, ethyl, morpholinoethyl and branched 2-pyrrolidinoethyl esters were considerably more stable (half-lives between 41 and 116 min, compared to <5 min). Inhibition by physostigmine indicated unspecific cholinesterases to be involved in the rapid ester cleavage. Due to lower protein content and higher enzymatic activity in murine compared to human plasma, reduced stability of all investigated esters in mouse plasma (t(1/2) <2 min) has to be taken into account with respect to the design of animal studies. (C) 2014 Elsevier B.V. All rights reserved.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | HUMAN-SERUM-CHOLINESTERASE; RANDOMIZED PHASE-III; MULTIPLE-MYELOMA; OLD DRUG; HYDROCHLORIDE; MELPHALAN; URINE; QUANTIFICATION; METABOLITES; VALIDATION; Bendamustine ester; Nitrogen mustard; Hydrolysis Butyrylcholinesterase; Ester cleavage |
| Subjects: | 500 Science > 540 Chemistry & allied sciences 600 Technology > 615 Pharmacy |
| Divisions: | Chemistry and Pharmacy > Institute of Pharmacy > Pharmaceutical/Medicinal Chemistry II (Prof. Buschauer) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 24 Jul 2019 11:31 |
| Last Modified: | 24 Jul 2019 11:31 |
| URI: | https://pred.uni-regensburg.de/id/eprint/5966 |
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