Pharmacokinetic Analysis of Four Bioactive Iridoid and Secoiridoid Glycoside Components of Radix Gentianae Macrophyllae and Their Synergistic Excretion by HPLC-DAD Combined with Second-Order Calibration
Natural Products and Bioprospecting
Pharmacokinetic Analysis of Four Bioactive Iridoid and Secoiridoid Glycoside Components of Radix Gentianae Macrophyllae and Their Synergistic Excretion by HPLC-DAD Combined with Second-Order Calibration
Tian-Ming Yang 0 1
Yang-Xi Liu 0 1
Hai-Yan Fu 0 1
Wei Lan 0 1
Han-Bo Su 0 1
He-Bin Tang 0 1
Qiao-Bo Yin 0 1
He-Dong Li 0 1
Li-Ping Wang 0 1
Hai-Long Wu 0 1
0 State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University , Changsha 410082 , China
1 The Modernization Engineering Technology Research Center of Ethnic Minority Medicine of Hubei Province, School of Pharmaceutical Sciences, South-Central University for Nationalities , Wuhan 430074 , China
An HPLC-DAD method combined with second-order calibration based on the alternating trilinear decomposition (ATLD) algorithm with the aid of region selection was developed to simultaneously and quantitatively characterize the synergistic relationships and cumulative excretion of the four bioactive ingredients of Radix Gentianae Macrophyllae in vivo. Although the analytes spectra substantially overlapped with that of the biological matrix, the overlapping profiles between analytes and co-eluting interferences can be successfully separated and accurately quantified by the ATLD method on the basis of the strength of region selection. The proposed approach not only determined the content change but also revealed the synergistic relationships and the cumulative excretion in vivo of the four ingredients in urine and feces samples collected at different excretion time intervals. In addition, several statistical parameters were employed to evaluate the accuracy and precision of the method. Quantitative results were confirmed by HPLC-mass spectrometry. Satisfactory results indicated that the proposed approach can be utilized to investigate the pharmacokinetics of Radix Gentianae Macrophyllae excretion in vivo.
Graphical Abstract
HPLC-DAD
Second-order calibration Pharmacokinetic analysis
1 Introduction
Radix Gentianae Macrophyllae belongs to the Gentiana
genus of Gentianaceae and is widely used as a remedy in
traditional Chinese medicine (TCM) for more than
2000 years [
1
]. The dominant bioactive constituents in
Radix Gentianae Macrophyllae are iridoid and secoiridoid
glycosides, including gentiopicroside (GPS), loganic acid
(LOG), swertiamarin (SWM), and sweroside (SWS), which
exhibit analgesic, anti-inflammatory, antipyretic,
antirheumatic, diuretic, febrifuge, and hypoglycemic
pharmacological effects for treating hypotension, rheumatism, pains,
fever, and allergic inflammations [
2–6
].
Unlike those of chemical drugs, the therapeutic effects
of TCM are based on the synergistic effect of their
bioactive compounds [
7
]. The determination of several
components can not sufficiently represent the effects of
TCM [
8
], whereas multi-component analysis helps reveal
the effect of coordination among the TCM components
[
9, 10
]. Thus, simultaneous quantification of bioactive
ingredients in a complex physiological matrix is crucial.
Pharmacokinetics describes how the body affects a
specific drug after administration through absorption and
distribution, the chemical changes of the substance in the
body, and the excretion effects and routes of metabolites in
the drug [
11
]. Pharmacokinetic study on multiple
components is a difficult field in TCM research because of the
complicated and microscale nature of the chemical
components of TCM.
Based on the available literature, several analytical
methods, such as HPLC-UV [
12, 13
], UFLC-MS/MS [14],
and LC/MS/MS [
15
], are available for quantifying
bioactive ingredients derived from Radix Gentianae
Macrophyllae in a biological matrix. Chromatographic analysis is
an effective strategy to directly determine drugs. However,
baseline drift and overlapping of peaks between matrix
constituents and compounds of interest often occur in the
chromatographic analysis of complex samples. For
eliminating the influence of interfering compounds on
analytes of interest, complex gradient elution is employed
to isolate analytes. Several trivial sample pretreatments and
instrumental parameters require optimization, entailing
considerable energy, time, and cost.
Second-order calibration is widely used in numerous
scientific areas, such as food quality and safety [
16–24
],
cosmetic research [
25, 26
], environmental monitoring
[
27–30
], biochemical assay [
31–37
], and routine analysis
[
38–40
]. The strategy is a good solution to the previously
mentioned problems because the concentrations of
individual components can be accurately obtained even in the
presence of uncalibrated interferences, that is,
‘‘secondorder advantage.’’ Pharmacokinetic research on TCM is
always performed using chromatographic technique, which
offers advantages of powerful separation and analysis
capabilities. However, an extremely complex gradient (...truncated)