Development of a sensitive liquid chromatography-electrospray ionization tandem mass spectrometry method for the measurement of 7-cyanoquinocarcinol in human plasma.
A sensitive method for the determination of an anti-cancer agent, DX-52-1 (7-cyanoquinocarcinol, I) and quinocarmycin (II) which is formed from I either by metabolism or degradation, in human plasma has been developed utilising liquid chromatography electrospray-ionization tandem mass spectrometry (LC-ESI-MS-MS). The procedure involves solid-phase extraction at pH 2 and low temperature (4-6 degrees C) to prevent the decomposition of I to II, the separation by reversed-phase HPLC and the multiple reaction monitoring (MRM) by ESI-MS-MS. The mean precision and accuracy at the lower limit of quantitation (LLOQ) of I, 0.25 ng ml(-1), were 8.7% and - 10.8%, respectively. Since an interfering peak eluting slightly earlier than II was observed on the HPLC of blank plasma, the LLOQ of II was set at 5 ng ml(-1) where the mean precision and accuracy were 15.6% and -9.8%. The results suggested that the method is useful for the simultaneous monitoring of I and II in the clinical trials of I.
Yamaguchi
K
K
Drug Development Research Laboratories, Pharmaceutical Research Institute, Kyowa Hakko Kogyo Co., Ltd., Japan.
Fuse
E
E
Takashima
M
M
Yasuzawa
T
T
Kuwabara
T
T
Kobayashi
S
S
D000903:Antibiotics, Antineoplastic / Q000097:blood*; D002853:Chromatography, Liquid; D006801:Humans; D007546:Isoquinolines / Q000097:blood; D008297:Male; D013058:Mass Spectrometry; D012680:Sensitivity and Specificity
D000903:Antibiotics, Antineoplastic; D007546:Isoquinolines; C091971:DX 52-1; C038710:quinocarcin