Bioanalytical method development and validation for a large peptide HIV fusion inhibitor (Enfuvirtide, T-20) and its metabolite in human plasma using LC-MS/MS.

Abstract:

:A method for measuring a human immunodeficiency virus (HIV) cell membrane fusion inhibitor (T-20/Ro 29-9800) and its metabolite (M-20/Ro 50-6343) in human plasma by liquid chromatography tandem mass spectrometry (LC-MS/MS) was developed. The relatively large peptide analytes and their corresponding deuterated (d(10)) peptides used as internal standard were isolated from plasma by protein precipitation with two volumes of acetonitrile to plasma. A large pore size reversed-phase C(18) column was employed to elute the peptides. A triple quadrupole mass spectrometer with electrospray interface operating in positive ion and multiple reaction monitoring modes with transitions m/z 1124-->1343 for both T-20 and M-20 was utilized for peak detection. The advantages of the method were a simple sample preparation, specific and sensitive MS/MS detection, and a wide dynamic range of 10-2000 ng/ml for T-20. The method was validated and used for analyzing samples from clinical studies to provide pharmacokinetic profiles of the HIV fusion inhibitor peptide drug and its metabolite.

journal_name

J Pharm Biomed Anal

authors

Chang D,Kolis SJ,Linderholm KH,Julian TF,Nachi R,Dzerk AM,Lin PP,Lee JW,Bansal SK

doi

10.1016/j.jpba.2005.01.024

subject

Has Abstract

pub_date

2005-07-01 00:00:00

pages

487-96

issue

3

eissn

0731-7085

issn

1873-264X

pii

S0731-7085(05)00073-7

journal_volume

38

pub_type

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