Determination of pyrrole-imidazole polyamide in rat plasma by liquid chromatography-tandem mass spectrometry.
Pyrrole (Py)-imidazole (Im) polyamides synthesized by combining N-methylpyrrole and N-methylimidazole amino acids have been identified as novel candidates for gene therapy. In this study, a sensitive method using liquid chromatography-tandem mass spectrometry (LC-MS/MS) with an electrospray ionization (ESI) source was developed and validated for the determination and quantification of Py-Im polyamide in rat plasma. Py-Im polyamide was extracted from rat plasma by solid-phase extraction (SPE) using a Waters Oasis HLB cartridge. Separation was achieved on an ACQUITY UPLC HSS T3 (1.8 microm, 2.1 x 50 mm) column by gradient elution using acetonitrile:distilled water:acetic acid (5:95:0.1, v/v/v) and acetonitrile:distilled water:acetic acid (95:5:0.1, v/v/v). The method was validated over the range of 10-1000 ng/mL and the lower limit of quantification (LLOQ) was 10 ng/mL. This method was successfully applied to the investigation of the pharmacokinetics of Py-Im polyamide after intravenous administration.
Nagashima
Takashi
T
Department of Clinical Pharmacokinetics, College of Pharmacy, Nihon University, Funabashi, Chiba 274-8555, Japan.
Aoyama
Takahiko
T
Fukasawa
Akiko
A
Watabe
Satoshi
S
Fukuda
Noboru
N
Ueno
Takahiro
T
Sugiyama
Hiroshi
H
Nagase
Hiroki
H
Matsumoto
Yoshiaki
Y
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D006863:Hydrogen-Ion Concentration; D007093:Imidazoles / Q000737:chemistry*; D007202:Indicators and Reagents; D008297:Male; D009757:Nylons / Q000737:chemistry*; D011758:Pyrroles / Q000737:chemistry*; D011786:Quality Control; D051381:Rats; D017208:Rats, Wistar; D012015:Reference Standards; D015203:Reproducibility of Results; D052616:Solid Phase Extraction; D021241:Spectrometry, Mass, Electrospray Ionization; D053719:Tandem Mass Spectrometry
D007093:Imidazoles; D007202:Indicators and Reagents; D009757:Nylons; D011758:Pyrroles