Identification of chemicals and their metabolites from PHY906, a Chinese medicine formulation, in the plasma of a patient treated with irinotecan and PHY906 using liquid chromatography/tandem mass spectrometry (LC/MS/MS).
Traditional Chinese Medicine (TCM) is increasingly being used in combination with Western medicine. In general, TCM is comprised of multiple components in sharp contrast to Western medicine, where a single active chemical is used. Presently, there are no well-established standards for most of the chemical compounds of TCM and their respective metabolites. Moreover, there are no formal analytical methods for the identification of these chemicals, especially in trace amounts. The ability to measure the pharmacokinetic behaviors of chemicals and their metabolites from these herbal formulations are critical in understanding of the action of TCM. This paper describes the use of LC/MS/MS along with enzyme treatments and n-octanol/water partition coefficient, to investigate the chemical components of PHY906 and their metabolites in the plasma of a patient with metastatic colorectal cancer (mCRC) treated with irinotecan and PHY906. The chemicals from an aqueous extract of PHY906 and the plasma from a patient was prepared and separated on an Agilent ZORBAX-SB C(18) column, and eluted with acetonitrile/0.05% (v/v) formic acid. From the PHY906 aqueous extract, a total of 57 compounds and 27 metabolites were identified and tentatively assigned structures based on their identified mass spectrometry, enzyme digestion and n-octanol/water partition coefficient. In contrast, analysis of patient plasma identified only 33 chemicals and new metabolites. These findings demonstrated that LC/MS/MS was and effective and reliable method for studying the parent chemicals of the Chinese herbal medicine PHY906 and their metabolites in a patient with metastatic colorectal cancer.
Zhang
Wei
W
Department of Pharmacology, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA.
Saif
Muhammad W
MW
Dutschman
Ginger E
GE
Li
Xin
X
Lam
Wing
W
Bussom
Scott
S
Jiang
Zaoli
Z
Ye
Min
M
Chu
Edward
E
Cheng
Yung-Chi
YC
D000097:Acetonitriles / Q000737:chemistry; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D002853:Chromatography, Liquid / Q000379:methods*; D015179:Colorectal Neoplasms / Q000188:drug therapy; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000378:metabolism* / Q000493:pharmacokinetics / Q000627:therapeutic use; D005561:Formates / Q000737:chemistry; D006801:Humans; D000077146:Irinotecan; D053719:Tandem Mass Spectrometry / Q000379:methods*
D000097:Acetonitriles; D004365:Drugs, Chinese Herbal; D005561:Formates; C476037:PHY 906; C030544:formic acid; D000077146:Irinotecan; D002166:Camptothecin; C032159:acetonitrile