Premium
An LC/MS Method for the Detection of the Bispyridinium Oxide MMB‐4
Author(s) -
Byers Christopher,
Smith John Richard,
Bass Nikki,
Basile Nicole,
Capacio Benedict
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a100-d
Subject(s) - chromatography , chemistry , pharmacokinetics , mass spectrometry , dilution , liquid chromatography–mass spectrometry , pharmacology , medicine , physics , thermodynamics
The bispyridinium oxime MMB‐4 has been shown to be more effective than pralidoxime chloride (2‐PAM) against exposure from organophosphonate nerve agent compounds. To examine the pharmacokinetics of this compound, an assay using guinea pig plasma has been developed utilizing liquid chromatography‐mass spectrometry (LC‐MS). Sample preparation involved the addition of internal standard (IS) 2‐PAM (10 ul; 1.25 ug/ml) followed by a 10‐fold dilution with purified water. The sample was subsequently centrifuged, and 5 ul of the supernatant removed and injected for analysis. Calibration curves of peak area ratios (MMB‐4/IS) versus concentration (1.56‐100.0 ug/ml) displayed a linear relationship (r 2 = 0.9950) and %CV of less than 15%. The accuracy and precision of this method were assessed through the intra‐ and inter‐day variability of six test unknown samples (2.34–75.0 ug/ml). For intra‐day samples (n=6) the accuracy was found to range from 86.5 – 99.3%, while the precision, as expressed by %CV, was less than 14.8%. Inter‐day unknown sample (n=6) results exhibited accuracy of 85.0–99.6% and %CV less than 15%. The MMB‐4 was stable in frozen plasma for up to 14 days and in frozen prepared samples for up 3 weeks. Prepared samples of MMB‐4‐spiked plasma remained stable at room temperature for up to hours. Data indicate that the LC/MS method suitable for examining the pharmacokinetics of MMB‐4 in guinea pigs.