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Determination of BAPTA-AM, the Acetoxymethyl Tetraester of BAPTA, in Rat Plasma by Liquid Chromatography Tandem Mass Spectrometry

Determination of BAPTA-AM, the Acetoxymethyl Tetraester of BAPTA, in Rat Plasma by Liquid Chromatography Tandem Mass Spectrometry

Feng Zheng, Taijun Hang, Chunyong Wu, Bin Di, Wenyin Liu, Jihua Xu, Chunxiao Zhai, Di Sun, Jinxing Liu, Wei Wei

J Mass Spectrom. 2006 Dec;41(12):1615-22.

PMID: 17103492

Abstract:

BAPTA-AM is the acetoxymethylester of the calcium chelator BAPTA and has demonstrated efficacy in several animal models of cerebral ischemia. This paper describes the development of a method for the determination of BAPTA-AM in rat plasma by liquid chromatography/tandem mass spectrometry. Owing to multiple ester groups in the structure of BAPTA-AM, [M + Na](+) was chosen as the analytical ion for quantification of BAPTA-AM. During the analytical method development, a high percentage of organic solvent and the addition of an amount of sodium acetate and formic acid in the mobile phase were found to favor the sensitivity and reproducibility of [M + Na](+). Poor fragmentation was usually observed in the MS/MS spectra of sodium adduct ions. However, abundant and reproducible fragment ions were observed for the BAPTA-AM sodium adduct ion, and therefore the traditional selective reaction-monitoring mode was used to further improve the sensitivity of MS detection. Because of the lability of the ester bond, a combination of fluoride and hydrochloric acid was applied to minimize the enzymatic hydrolysis, and acetonitrile was chosen to avoid the chemical hydrolysis or solvolysis during the sample collection and preparation procedure. On the basis of these studies, a rapid, sensitive and reproducible method for the determination of BAPTA-AM in rat plasma, using LC/ESI-MS/MS and a simple protein precipitation procedure, was developed and validated. Also, the present method was successfully applied to the determination of BAPTA-AM plasma concentrations for pharmacokinetic studies in rats.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP126150978-B	BAPTA-AM		126150-97-8	Price

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