Determination of LY355703 in dog and mouse plasma by positive ion liquid chromatography/tandem mass spectrometry with atmospheric pressure chemical ionization

✍ Scribed by Berna, M.; Shugert, R.; Mullen, J.

• Publisher: John Wiley and Sons
• Year: 1998
• Tongue: English
• Weight: 268 KB
• Volume: 33
• Category: Article
• ISSN: 1076-5174
• DOI: 10.1002/(sici)1096-9888(199802)33:2<138::aid-jms617>3.0.co;2-7

✦ Synopsis

A liquid chromatographic/mass spectrometric assay was developed for the determination of LY355703, a potent anti-tumor drug, in mouse and dog plasma. Empore (3M)

solid-phase extraction cartridges were used for C 18 sample preparation in conjunction with a positive pressure manifold. Chromatographic separation was obtained with a cyano high-performance liquid chromatographic column and detection was conducted using atmospheric pressure chemical ionization tandem mass spectrometry in the selected reaction monitoring mode. A structural analog, compound LY354504, was used as the internal standard. The assay was validated for the determination of LY355703 in mouse (ICR and NuNu) and dog (beagle) plasma. The lower and upper limits of quantitation were 2.1 and 527 ng ml-1, respectively, using a 0.1 ml plasma aliquot. The signal-to-noise ratio of a typical 2.1 ng ml-1 standard was ¿40 : 1. The inter-day precision (relative standard deviation) and accuracy (relative error) derived from the analysis of validation samples at Ðve concentrations ranged from 2.7 to 7.6% and from 4.8 to 4.5% , respectively. Throughput is approximately one sample every 3 min. This assay is simple, sensitive, accurate, precise and is being used to support toxicokinetic studies in dog and mouse.