Towards Polypharmacokinetics: Pharmacokinetics of Multicomponent Drugs and Herbal Medicines Using a Metabolomics Approach

Table 1

Summary of PK studies of single chemicals and multicomponent drugs or herbal medicines using metabolomics.

Substance	Type of biological sample	Bioanalysis technique	Multivariate analysis method	Reference
GSK-X	Rat urine	LC-TOFMS	PCA, Ward’s HCA	[29]
Citalopram	Rat urine	LC-MS	PCA, PLS, PARAFAC, N-PLS	[30]
Ferulic acid and sinapic acid	Rat urine	HPLC-QTOFMS	PLS-DA	[38]
Fenofibrate	Rat urine	UPLC-QTOFMS	PLS-DA	[47]
Isoliquiritigenin	Rat urine	UPLC-QTOFMS	PCA, PLS-DA	[56]
Tolcapone	Rat urine	UPLC-QTOFMS	PCA	[49]
Acetaminophen	Rat urine	UPLC/MS, NMR	PCA, PLS-DA	[41]
Valproic acid	Mouse urine	LC-MS	PCA	[53]
ThioTEPA	Mouse urine	UPLC-QTOFMS	OPLS	[55]
NSC686288 (aminoflavone)	Mouse urine	UPLC-QTOFMS	PCA	[31, 34]
Ethanol	Mouse urine	UPLC-QTOFMS	PLS-DA, OPLS	[57]
Arecoline and arecaidine	Mouse urine	UPLC-QTOFMS	PCA, PLS-DA	[35]
(±)-Arecoline 1-oxide	Mouse urine	UPLC-QTOFMS	PCA	[37]
PhIP*	Mouse urine	UPLC-QTOFMS	PCA	[36]
Acetaminophen	Mouse urine	UPLC-QTOFMS	PCA	[39]
Cyclophosphamide/ifosfamide	Mouse urine	UPLC-QTOFMS	OPLS	[50]
Vitamin E	Mouse urine	UPLC-TOFMS	PCA, PLS-DA	[46]
Melatonin	Mouse urine	IPLC-TOFMS, LC-MS/MS	PCA, OPLS	[44]
Tipranavir	Mouse urine, feces, tissue	UPLC-TOFMS	PCA, OPLS-DA	[51]
Ritonavir	Mouse urine and feces	UPLC-TOFMS	OPLS-DA	[54]
Procainamide	Mouse and human urine	UPLC-QTOFMS	PCA, PLS-DA	[58]
Fenofibrate	Monkey urine	UPLC-QTOFMS	PLS-DA	[48]
Pulegone/clozapine	Mouse liver	UPLC-TOFMS	PCA, OPLS-DA	[42]
Dextromethorphan	Human urine	LC-MS/MS	PCA, OPLS-DA	[43]
3,4-Dehydro-debrisoquine	Human urine	UPLC-QTOFMS	OPLS	[31, 59]
Cocoa powder	Human urine	HPLC-QTOFMS	PLS-DA, two-way HCA	[60]
Almond skin extract	Human urine	LC-QTOFMS	PCA, OPLS-DA	[61]
Pu-erh tea	Human urine	UPLC-QTOFMS, GC-TOFMS	PCA, OPLS-DA	[6, 62]
A mix of wine extract and grape juice extract	Human urine	^1H NMR	ANOVA-PCA/PLS	[63]
Dried black tea extract and red grape extract	Human urine	^1H NMR	ANOVA-PCA/PLS	[64]
Chamomile tea	Human urine	^1H NMR	PCA, PLS, OSC	[14]
Dark chocolate	Human urine, plasma	^1H NMR, LC-MS, LC-MS/MS	PCA, OPLS-DA	[65]
Nefazodone	NADPH-supplemented human liver microsomal incubation samples	LC-MS	PCA	[52]
Rifampicin, phenobarbital, and CITCO**	Human hepatocytes	UPLC-TOFMS	PCA, OPLS, SUS plot	[66]

∗2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine.
**6-(4-Chlorophenyl)imidazo[2,1-b][1,3]thiazole-5-carbaldehydeO-3,4-dichlorobenzyl) oxime.
LC-MS: liquid chromatography-mass spectrometry; UPLC-QTOFMS: ultraperformance liquid chromatography-quadrupole time of flight mass spectrometry; NMR: nuclear magnetic resonance; GC-TOFMS: gas chromatography-time of flight mass spectrometry; PCA: principle component analysis; PLS: partial least squares; OPLS-DA: orthogonal partial least squares-discriminant analysis; DAPARAFAC: parallel factor analysis; N-PLS: multilinear partial least squares; OSC: orthogonal signal correction.