LC-MS/MS Method for the Quantitative Determination of Tanespimycin and its Active Metabolite in Human Plasma: Method Validation and Overcoming an Insidious APCI Source Phenomenon

Morse Faria, O. Ismaiel, James Waltrip, Thomas Mariannino, Moucun Yuan, W. Mylott, V. Roongta, Jim X. Shen, Pathanjali Kadiya
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Abstract

RESULTS: A sensitive method was developed and validated for the measurement of tanespimycin and its active 17-AG in human plasma using tanespimycin -C3, 15N as an internal standard. The assay was validated over the concentration range of 10.0 to 2500 ng/mL for tanespimycin and 5.00 to 1250 ng/mL for 17-AG. During method development, an internal standard variability due to an in-source reduction of the quinone moiety during ionization was observed. The in-source reduction was mitigated by selection of appropriate mobile phases, internal standard concentration, injection volume, source temperature, and continuous maintenance of the source between runs.
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LC-MS/MS法定量测定人血浆中丹那霉素及其活性代谢物:方法验证及克服APCI源隐匿现象
结果:建立了以tanesimycin -C3, 15N为内标测定人血浆中tanesimycin及其活性17-AG的灵敏方法。在10.0 ~ 2500 ng/mL的浓度范围内验证了该方法,在5.00 ~ 1250 ng/mL的浓度范围内验证了该方法。在方法开发过程中,观察到由于电离过程中醌部分的源内减少而引起的内部标准变异性。通过选择合适的流动相、内标准浓度、进样量、源温度以及在运行之间持续维护源,可以减轻源内减少。
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