Use of trifluoroacetic acid to quantify small, polar compounds in rat plasma during discovery-phase pharmacokinetic evaluation.

Use of trifluoroacetic acid to quantify small, polar compounds in rat plasma during discovery-phase pharmacokinetic evaluation. Research Abstract Details 

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Use of trifluoroacetic acid to quantify small, polar compounds in rat plasma during discovery-phase pharmacokinetic evaluation. Abstract Text:

M J Bock,K L Neilson,A Dudley,M J Bock,K L Neilson,A Dudley,

Although it is accepted that trifluoroacetic acid (TFA) can cause suppression of an analyte during LC/MS analysis, this paper presents a relatively sensitive gradient method that uses a TFA mobile phase for the improved quantification of small, polar drug-like compounds. The described method was developed in a discovery drug metabolism and pharmacokinetics (DMPK) laboratory for the screening measurement of compound concentrations to calculate PK parameters and CNS exposure of compounds from a chemical series that had poor chromatography under generic methods using formic acid mobile phase. The samples were collected by a Culex automated sampling unit, and the plasma proteins were precipitated by a Tecan robot in 96-well plates. After centrifugation, the supernatant was removed, dried down using a SPE-Dry unit, and the samples were reconstituted in aqueous buffer on the robot. The samples were analyzed on an Agilent LC/MSD using a 5-min gradient on a 5 cm phenyl column. No additional steps, such as the "TFA-fix", were necessary. Although sample batches were analyzed over 6h, no drift or degradation of signal was observed. The improved chromatography resulted in a method that was selective, rugged, and had a dynamic range from 5 to 20,000 nM, which was sufficient to quantitate low volume, serial plasma samples collected out to 8 h postdose.

Use of trifluoroacetic acid to quantify small, polar compounds in rat plasma during discovery-phase pharmacokinetic evaluation. Publishing Authors By Initials

MJ Bock,KL Neilson,A Dudley,MJ Bock,KL Neilson,A Dudley,

For similar organic chemicals: carboxylic acids: acids, acyclic: acetic acids: trifluoroacetic acid research abstracts see: organic chemicals: carboxylic acids: acids, acyclic: acetic acids: trifluoroacetic acid research

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Use of trifluoroacetic acid to quantify small, polar compounds in rat plasma during discovery-phase pharmacokinetic evaluation. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Journal of chromatography. B, Analytical technolog

VOLUME: 856

Page Numbers: 165-70

Journal Abbreviation: J. Chromatogr. B Analyt. Techn

ISSN: 1570-0232

DAY: 2

MONTH: 06

YEAR: 2007

Use of trifluoroacetic acid to quantify small, polar compounds in rat plasma during discovery-phase pharmacokinetic evaluation. Information

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LANGUAGE: eng

NlmUniqueID: 101139554

Use of trifluoroacetic acid to quantify small, polar compounds in rat plasma during discovery-phase pharmacokinetic evaluation. Keywords Mesh Terms:

KEYWORDS: Trifluoroacetic Acid

MESH TERMS: chemistry

Chemical & Substance for Abstract: Use of trifluoroacetic acid to quantify small, polar compounds in rat plasma during discovery-phase pharmacokinetic evaluation. Information

Substance Name: Trifluoroacetic Acid

Registry Number: 76-05-1

Grant and Affiliation Information for Use of trifluoroacetic acid to quantify small, polar compounds in rat plasma during discovery-phase pharmacokinetic evaluation.

AFFILIATION: AstraZeneca, Discovery DMPK, 1800 Concord Pike, Wilmington, DE 19803, United States. Mary.Bock@AstraZeneca.com

Country: Netherlands

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MEDLINETA: J Chromatogr B Analyt Technol

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