An electrochemical method based on a directly electrochemically reduced graphene oxide (ERGO) film coated on a glassy carbon electrode (GCE) was developed for the rapid and convenient determination of rutin in pla...An electrochemical method based on a directly electrochemically reduced graphene oxide (ERGO) film coated on a glassy carbon electrode (GCE) was developed for the rapid and convenient determination of rutin in plasma. ERGO was modified on the surface of GCE by one-step electro-deposition method. Electrochemical behavior of rutin on ERGO/GCE indicated that rutin underwent a surface-controlled quasi-reversible process and the electrochemical parameters such as charge transfer coefficient (α), electron transfer number (n) and electrode reaction standard rate constant (ks) were 0.53, 2 and 3.4 s -1, respectively. The electrochemical sensor for rutin in plasma provided a wide linear response range of 4.70 × 10 ^-7 1.25 × 10^-5 M with the detection limit (s/n=3) of 1.84 × 10^-8 M. The assay was success- fully used to the pharmacokinetic study of rutin. The pharmacokinetic parameters such as elimination rate half-life (t1/2), area under curve (AUC), and plasma clearance (CL) were calculated to be 3.345 ± 0.647 rain, 5750 ±656.0 μg min/mL, and 5.891± 0.458 mL/min/kg, respectively. The proposed method utilized a small sample volume of 10 μL and had no complicated sample pretreatment (without deproteinization), which was simple, eco-friendly, and time- and cost-efficient for rutin pharmacokinetic studies.展开更多
Three extraction methods were compared for their efficiency to analyze sitagliptin and simvastatin in rat plasma by LC-MS/MS, including (1) liquid-liquid extraction (LLE), (2) solid phase extraction (SPE) and ...Three extraction methods were compared for their efficiency to analyze sitagliptin and simvastatin in rat plasma by LC-MS/MS, including (1) liquid-liquid extraction (LLE), (2) solid phase extraction (SPE) and (3) supported liquid extraction (SLE). Comparison of recoveries of analytes with different extraction methods revealed that SLE was the best extraction method. The detection was facilitated with ion trap-mass spectrometer by multiple reactions monitoring (MRM) in a positive ion mode with ESI. The transitions monitored were m./z 441.1→325.2 for simvastatin, 408.2→235.1 for sitagliptin and 278.1→260.1 for the IS. The lower limit of quantification (LLOQ) was 0.2 ng/mL for sitagliptin and 0.1 ng/mL for simvastatin. The effective SLE offers enhanced chromatographic selectivity, thus facilitating the potential utility of the method for routine analysis of biological samples along with pharmacokinetic studies.展开更多
A novel bioanalytical method was developed and validated for the quantitative determination of darunavir(DRV) in rat plasma by employing hydrophilic interaction chromatography and tandem mass spectrometry(HILIC-MS...A novel bioanalytical method was developed and validated for the quantitative determination of darunavir(DRV) in rat plasma by employing hydrophilic interaction chromatography and tandem mass spectrometry(HILIC-MS/MS) with supported liquid extraction(SLE).lrbesartan(IRB) was used as an internal standard(IS).The analyte in rat plasma(200 μL) was isolated through SLE using ethyl acetate as the eluting solvent.The chromatographic separation was achieved on Luna-HILIC(250 mm × 4.6 mm,5 μm)column with a mobile phase of 0.1% of formic acid in water:acetonitrile(5:95,v/v),at a constant flow rate of 1.0mL/min.The MS/MS ion transitions for DRV(548.1→392.0) and IS(429.2→207.1) were monitored on an ion trap mass spectrometer,operating in the multiple reaction monitoring(MRM) mode.The lower limit of quantitation(LLOQ) was 0.2 ng/mL and quantitation range was 0.2-5000 ng/mL.The method was validated for its selectivity,sensitivity,carryover,linearity,precision,accuracy,recovery,matrix effect and stability.The method was successfully applied to pharmacokinetic study in rats.展开更多
Poliumoside is the main active constituent of Callicarpa kwangtungensis Chun (CK), a traditional Chinese medicine for management of hemostasis. In this study, a rapid and selective ultra-performance liquid chromatogra...Poliumoside is the main active constituent of Callicarpa kwangtungensis Chun (CK), a traditional Chinese medicine for management of hemostasis. In this study, a rapid and selective ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC/ Q-TOF-MS) method was developed and validated to quantify poliumoside in rat plasma. The targeted analytes in rat plasma were prepared through protein-precipitation method using 10% trichloroacetic acid (TCA). The chromatographic separation was performed on a Waters BEH C<sub>18</sub> column (2.1 × 100 mm, 1.7 μm) by acetonitrile-water containing 0.1% formic acid. The calibration curve was linear over the range of 50 - 10,000 ng/mL (r<sup>2</sup> > 0.99). The intra-day or inter-day precision was less than 7.97% and accuracy was within ?7.00% - 3.36%. The developed method was successfully applied to pharmacokinetic study of poliumoside in rat plasma. Although being rapidly absorbed (T<sub>max</sub> ≤ 30 min), poliumoside was poorly bioavailable after oral administration (the absolute bioavailability was only 0.69%).展开更多
Management of cardiovascular risk factors in diabetes demands special attention due to their co-existence. Pioglitazone (PIO) and telmisartan (TLM) combination can be beneficial in effective control of cardiovascu...Management of cardiovascular risk factors in diabetes demands special attention due to their co-existence. Pioglitazone (PIO) and telmisartan (TLM) combination can be beneficial in effective control of cardiovascular complication in diabetes. In this research, we developed and validated a high throughput LC-MS/MS method for simultaneous quantitation of PIO and TLM in rat plasma. This developed method is more sensitive and can quantitate the analytes in relatively shorter period of time compared to the previously reported methods for their individual quantification. Moreover, till date, there is no bioanalytical method available to simultaneously quantitate PIO and TLM in a single run. The method was validated according to the USFDA guidelines for bioanalytical method validation. A linear response of the analytes was observed over the range of 0.005-10 pg/mL with satisfactory precision and accuracy. Accuracy at four quality control levels was within 94.27%-106.10%. The inlxa- and inter-day precision ranged from 2.32% to 10.14% and 5.02% to 8.12%, respectively. The method was reproducible and sensitive enough to quantitate PIO and TLM in rat plasma samples of a preclinical pharmacokinetic study. Due to the potential of PIO-TLM combination to be therapeutically explored, this method is expected to have significant usefulness in future.展开更多
A novel isocratic reverse phase high performance liquid chromatography (RP-HPLC) with photo diode array (PDA) detection method for the determination of dobutamine (DBT) in rat plasma was developed and validated ...A novel isocratic reverse phase high performance liquid chromatography (RP-HPLC) with photo diode array (PDA) detection method for the determination of dobutamine (DBT) in rat plasma was developed and validated after optimization of various chromatographic conditions and other experimental parameters. Homoveratrylamiue was used as an internal standard. Methanol was used as the extracting solvent for the preparation of plasma samples. Samples were separated on a Symmetry C18 (250ram x4.6mm i.d., 5 pro) analytical column. Acetonitrile and 15raM potassium dihydrogen phosphate (pH 5.0 with 0.3% TEA) (20:80, v/v) was used. The column oven temperature was optimized at 35 ~C and the flow rate was 0.8 mL/min. The detection wavelength was fixed at 230 nm for entire analysis. The calibration curve was found to be linear over the concentration range of 50-2000 ng/mL (ra=0.9992). The limit of quantification (LOQ) of the method was 50 ng/mL. The % RSD values of accuracy and precision values for intra and inter days were 〈 15% at quality control (QC) concentrations. Recovery, stability and robustness were studied within the acceptable range according to ICH guidelines. The method was efficiently applied to a pharmacokinetic study in healthy Wistar rats.展开更多
A simple, sensitive and selective method of high-performance liquid chromatography (HPLC) has been successfully developed for separation of bavachinin enantiomers in Fructus Psoraleae and rat plasma. The separation ...A simple, sensitive and selective method of high-performance liquid chromatography (HPLC) has been successfully developed for separation of bavachinin enantiomers in Fructus Psoraleae and rat plasma. The separation and detection conditions of HPLC were optimized. Chiral bavachinin were separated with the mobile phase of methanol and water (70:30, v/v) at a flow rate of 1.0 mL/min. The linear ranges were in the range of 20-1000 μg/mL. The detection limits were tested as 4 ng/mL and 6 ng/mL for (+)-bavachinin and (-)-bavachinin, respectively. The method has been applied to analyze chiral bavachinin in rat plasma. HPLC-MS method was used to test the accuracy.展开更多
A simple, rapid and sensitive method based on an ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) has been developed and validated for the determination of pimavanserin in rat plasma. Th...A simple, rapid and sensitive method based on an ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) has been developed and validated for the determination of pimavanserin in rat plasma. The analyte was extracted by protein precipitation with methanol and separated on an ACQUITY BEH C18 column (100 mm × 2.1 mm, 1.7μm; Waters, USA), with an isocratic elution of acetonitrile-water containing 10 mM ammonium acetate (70:30, v/v), at a flow rate of 0.2 mL/min for 2.5 rain. The analyte and clarithromyein (the internal standard) were detected and quantified in positive ion mode using multiple reaction monitoring transitions at m/z 428.2 - 223.0 for pimavanserin and m/z 748.5 - 589.5 for clarithromycin. Relative coefficient (r) for the calibration curve was more than 0.9980. The intra-day and inter-day precisions (relative standard deviation, RSD%) were less than 13.3% and 10.5%, respectively, and the accuracy (relative error, RE%) was within ± 11.5%. The analytical method was successfully applied to a routine pharmacokinetic study of pimavanserin in rats after oral administration at the dose of 10 mg/kg.展开更多
Deoxyglycychloxazol (TY501) is a glycyrrhetinic acid derivative which exhibits high anti-inflammatory activity and reduced pseudoaldosteronism compared to glycyrrhetinic acid. In this study, a sensitive and rapid li...Deoxyglycychloxazol (TY501) is a glycyrrhetinic acid derivative which exhibits high anti-inflammatory activity and reduced pseudoaldosteronism compared to glycyrrhetinic acid. In this study, a sensitive and rapid liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was established for the quantitation of TY501 in rat plasma. Plasma samples were treated by precipitating protein with methanol and supernatants were separated by a Symmetry C8 column with the mobile phase consisting of methanol and 10 mM ammonium formate (containing 0.1% of formic acid) (90:10, v/v). The selected reaction monitoring (SRM) transitions were performed at m/z 647.4→191.2 for TY501 and m/z 473.3→143.3 for astragaloside aglycone (IS) in the positive ion mode with atmospheric pressure chemical ionization (APCI) source. Calibration curve was linear over the concentration range of 5-5000 ng/mL. The lower limit of quantification was 5 ng/mL. The mean recovery was over 88%. The intra- and inter-day precisions were lower than 6.0% and 12.8%, respectively, and the accuracy was within ± 1.3%. TY501 was stable under usual storage conditions and handling procedure. The validated method has been successfully applied to a pharmacokinetic study after oral administration of TY501 to rats at a dosage of 10 mg/kg.展开更多
A high performance liquid chromatographic method was developed and validated for the quantitative determination of catechin in rat plasma and its pharmacokinetic study after intragastric administration of Catechu and ...A high performance liquid chromatographic method was developed and validated for the quantitative determination of catechin in rat plasma and its pharmacokinetic study after intragastric administration of Catechu and Xiongdanjiangre Wan into SD rats. Plasma samples were prepared by protein precipitation using methanol-5% aqueous zinc sulfate (70:30, v/v) as precipitant. Chromatographic separation was achieved on Hypersil Cl8 column (250 mm~ 4.6 mm, 10 pm) with acetonitrile-water-triethylamine (6:94:0.3, v/v/v, pH 4.0+0.1, adjusted with phos- phoric acid) as mobile phase, followed by a UV detection at 207 nm. Good linearity was obtained over the range of 0.143-7.15 mg/L of catechin, with correlation coefficient of 0.9992. The method was simple, sensitive, accurate and reproducible and' has been successfully applied to the pharmacokinetic study of catechin in rat plasma.展开更多
Neomangiferin, a natural C-glucosyl xanthone, has recently received a great deal of attention due to its multiple biological activities. In this study, a rapid and sensitive ultra-high performance liquid chromatograph...Neomangiferin, a natural C-glucosyl xanthone, has recently received a great deal of attention due to its multiple biological activities. In this study, a rapid and sensitive ultra-high performance liquid chromatography tandem mass spectrometry(UHPLC–MS/MS) method for the quantification of neomangiferin in rat plasma was developed. Using chloramphenicol as an internal standard(IS), plasma samples were subjected to a direct protein precipitation process using methanol(containing 0.05% formic acid). Quantification was performed by multiple reactions monitoring(MRM) method, with the transitions of the parent ions to the product ions of m/z 583.1-330.9 for NG and m/z 321.1-151.9 for IS. The assay was shown to be linear over the range of 0.2–400 ng/m L, with a lower limit of quantification of 0.2 ng/m L. Mean recovery of neomangiferin in plasma was in the range of 97.76%–101.94%. Relative standard deviations(RSDs) of intra-day and inter-day precision were both o 10%. The accuracy of the method ranged from94.20% to 108.72%. This method was successfully applied to pharmacokinetic study of neomangiferin after intravenous(2 mg/kg) and intragastric(10 mg/kg) administration for the first time. The oral absolute bioavailability of neomangiferin was estimated to be 0.53% 7 0.08% with an elimination half-life(t_(1/2)) value of 2.747 0.92 h, indicating its poor absorption and/or strong metabolism in vivo.展开更多
A rapid, simple and sensitive ultra-high performance liquid chromatography–tandem mass spectrometric(UPLC–MS/MS) method was developed and validated for the determination of hederasaponin B, an active triterpenoid sa...A rapid, simple and sensitive ultra-high performance liquid chromatography–tandem mass spectrometric(UPLC–MS/MS) method was developed and validated for the determination of hederasaponin B, an active triterpenoid saponin widely existed in Hedera helix L. Plasma samples were processed by protein precipitation with acetonitrile and separated on a Thermo Hypersil GOLD C18(2.1 mm × 50 mm,1.9 μm) at flow rate of 0.3 ml/min, with a gradient elution consisting of acetonitrile and water containing 0.1%(v/v) formic acid at 30 ℃ and detected by electrospray ionization mass spectrometry in the positive multiple reaction monitoring(MRM) mode. The linearity was found to be within the concentration range of 0.5–5000 ng/ml with a lower limit of quantification of 0.5 ng/ml. The absolute oral bioavailability of hederasaponin B was 0.24 ± 0.49%. This indicated that the concentration-time course of the hederasaponin B existed a double-peak phenomenon. This method was further applied to the determination of hederasaponin B in rat plasma and showed good practicability, for the first time, after intragastric(25 mg/kg) and intravenous(2 mg/kg) administration in rats.展开更多
Context: Broussonetia papyrifera (L.) Vent. (Moraceae), a traditional Chinese medicinal herb, has been extensively applied for many years to treat various diseases. Its fruits (Fructus Broussonetiae) have been commonl...Context: Broussonetia papyrifera (L.) Vent. (Moraceae), a traditional Chinese medicinal herb, has been extensively applied for many years to treat various diseases. Its fruits (Fructus Broussonetiae) have been commonly used as an important tonic for the treatment of age-related disorders with long history;recent research has proved that it contains 32% to 35% fixed oils. The fixed oil is composed mainly of unsaturated fatty acids, including linoleic acid, methyl palmitate, oleic acid and linoleic acid ester. Objective: To investigate the chemistry of the fatty oil from Fructus Broussonetiae (FOFB) and its effects on plasma lipids. Methods: The chemical composition of FOFB was examined and identified by GC-MS. Thirty male Wistar rats fed diet containing FOFB and cholesterol were studied for 28 days. The effect of dietary FOFB on plasma lipids and adipose tissue was tested. Results: Twelve compounds of FOFB were examined and identified, the major components of fatty oil, 8,11-octadecadienoic acid (83.75%), palmitic acid (10.22%), octadecadienoic acid (2.97%) and 9-octadecenoic acid (1.69%) were found. FOFB significantly exhibited the activities of decreasing the rat adipose tissue weight, triacylglycerol, total cholesterol, and low-density lipoprotein cholesterol (LDL-C) concentrations while the rat body weight remained unchanged. Discussion: FOFB contained a large amount of PUFA which had the effect on reducing plasma lipids and adipose.展开更多
AIMS: To develop an HPLC-MS/MS method for the quantification of platycodin D(PD) in rat plasma, and to acquire the main pharmacokinetic parameters of PD after oral administration of pure PD or of Platycodi Radix extra...AIMS: To develop an HPLC-MS/MS method for the quantification of platycodin D(PD) in rat plasma, and to acquire the main pharmacokinetic parameters of PD after oral administration of pure PD or of Platycodi Radix extract(PRE) containing PD. METHOD: Plasma samples were pretreated with solid-phase extraction using an Oasis HLB SPE cartridge. Madecassoside was used as the internal standard(IS). Chromatographic separation was achieved on an ODS column(100 mm × 2.1 mm i.d., 3.5 μm) with a mobile phase consisting of acetonitrile/water(30 : 70, V/V) containing 0.1 mmol L 1ammonium acetate at a flow rate of 0.25 mL min 1. The detection was performed on a triple quadruple tandem mass spectrometer using an electrospray ionization(ESI) source with a chromatographic run time of 3.0 min. The detection was operated by multiple reaction monitoring(MRM) of the transitions of m/z 1 223.6→469.2 for PD and of m/z 973.6→469.2 for madecassoside(IS), respectively. RESULTS: The calibration curve was linear from 5 to 2 000 ng mL 1(r2>0.99) with a lower limit of quantification(LLOQ) of 5 ng mL 1. The intra- and inter-day precision(relative standard deviation, RSD) values were below 15% and the accuracy(relative error, RE) was from 15% to +15% at three quality control(QC) levels. Plasma concentrations of PD were determined for 24 h after i.v. administration of PD, and oral administration of PD and PRE, respectively. The absolute oral bioavailability of PD in rats was found to be(0.48 ± 0.19)% when administered PD, and to be(1.81 ± 0.89)% when administered PRE. CONCLUSION: The developed HPLC-MS/MS method was successfully applied to assess the pharmacokinetic parameters and oral bioavailability of PD in rats after administration of PD and Platycodi Radix extract.展开更多
(E)-Methyl-4-aryl-4-oxabut-2-enoate(YH-8) is a novel PKn B protein kinase inhibitor with good anti-tuberculosis activity. To evaluate its pharmacokinetics in rats, a sensitive and selective high performance liquid chr...(E)-Methyl-4-aryl-4-oxabut-2-enoate(YH-8) is a novel PKn B protein kinase inhibitor with good anti-tuberculosis activity. To evaluate its pharmacokinetics in rats, a sensitive and selective high performance liquid chromatography–tandem mass spectrometric(LC–MS/MS) method has been developed and validated for the quantification of YH-8 in rat plasma for the first time. Samples were pre-treated using a liquid–liquid extraction with ethyl acetate and the chromatographic separation was performed on a C18 column by gradient elution with methanol–water as the mobile phase. YH-8 was detected using a tandem mass spectrometer in positive selected reaction monitoring(SRM) mode. Method validation revealed good linearity over the range of1–500 ng/m L for YH-8 with a lower limit of quantification(LLOQ) of 1 ng/m L. Intra- and inter-day precision of YH-8 assay in rat plasma samples were 2.0%–6.8%, with accuracy of the method being 100.69%–106.18%.Stability test showed that when spiked into rat plasma, YH-8 was stable for 12 h at room temperature, for up to15 days at -70℃, and after three freeze-thaw cycles. Extracted samples were found to be stable over 12 h in an auto-sampler. The method was successfully applied to the pharmacokinetic study of YH-8 in rats after oral administration at 100 mg/kg and 200 mg/kg.展开更多
Assays based on high-performance liquid chromatography(HPLC)and liquid chromatography tandem mass spectrometry(LC–MSn)have been developed and validated for the determination and metabolite identification of the bides...Assays based on high-performance liquid chromatography(HPLC)and liquid chromatography tandem mass spectrometry(LC–MSn)have been developed and validated for the determination and metabolite identification of the bidesmosidic triterpenoid saponin,BTS-1(3-O-β-D-galactopyranosyl-(1-2)-[β-D-xylopyranosyl-(1-3)]-β-D-glucuronopyranosyl gypsogenin 28-O-α-L-arabinopyranosyl-(1-3)-βD-xylopyranosyl-(1-4)-α-L-rhamnopyranosyl-(1-2)-β-D-fucopyranoside),in rat plasma.The assay was successfully applied to a pharmacokinetic study in rats given a single oral dose of BTS-1(400 mg/kg).The results indicated that the compound was rapidly absorbed(Tmax=1.2870.29 h,Cmax=37.475.6 mg/mL)and slowly eliminated(t1/2=13.276.6 h).In addition,secondary glycosides and aglycones of BTS-1 were detected and identified.Since these metabolites are known to be activeα-glucosidase inhibitors,they probably play an important role in mediating the pharmacological effects of the saponin.展开更多
Objective:The objective of the study was to develop a rapid and sensitive ultra-performance liquid chromatography-tandem mass spectrometric method for the determination of tetrandrine,fangchinoline,and cyclanoline in ...Objective:The objective of the study was to develop a rapid and sensitive ultra-performance liquid chromatography-tandem mass spectrometric method for the determination of tetrandrine,fangchinoline,and cyclanoline in rat plasma and to investigate their pharmacokinetics after oral administration of Stephaniae Tetrandrae Radix extracts.Methods:Sample pretreatment involved methanol pretreatment and liquid–liquid extraction of ethyl acetate from plasma with methanol.Tramadol was used as the internal standard.The analysis was performed using an high strength silica T3 column(100 mm×2.1 mm,1.8μm)and a gradient elution method consisting of mobile phase solution A(0.1%formic acid in water)and B(acetonitrile)at a flow rate of 0.4 mL/min.The detection was performed using a triple quadrupole tandem mass spectrometer in the multiple reaction monitoring mode and using an electrospray ionization source in the positive ionization mode.Results:High efficiency was achieved with an analysis time of 4 min/sample.The calibration curve linear in the concentration range of 1250 ng/ml(R^(2)≥0.9900)and the lower limit of quantification is 1 ng/ml.The intraday and interday precision(relative standard deviation)values were lower than 9.4.Accuracy(relative error)was within 10.3%at all three quality control levels.Conclusions:This method was successfully applied in pharmacokinetics of tetrandrine,fangchinoline,and cyclanoline in rats after oral administration of Stephaniae Tetrandrae Radix extracts.The maximum plasma concentration(C_(max))of tetrandrine,fangchinoline,and cyclanoline was 124.71±16.08,84.56±3.28,and 57.61±6.26 ng/mL,respectively.The time to reach C_(max)was 10.39±3.04 for tetrandrine,10.17±3.04 for fangchinoline,and 6.40±3.16 for cyclanoline.The pharmacokinetic results might help further guide the clinical application of Stephaniae Tetrandrae Radix.展开更多
<p> <strong>Short Retraction Notice</strong> </p> <p> The paper does not meet the standards of "American Journal of Analytical Chemistry". The article has been retracted d...<p> <strong>Short Retraction Notice</strong> </p> <p> The paper does not meet the standards of "American Journal of Analytical Chemistry". The article has been retracted due to the conflicts of interests between all authors to straighten the academic record. Aim is to promote the circulation of scientific research by offering an ideal research publication platform with due consideration of internationally accepted standards on publication ethics. The Editorial Board would like to extend its sincere apologies for any inconvenience this retraction may have caused. The full retraction notice in PDF is preceding the original paper, which is marked "RETRACTED". </p>展开更多
The present study was designed to develop and validate a rapid, sensitive, and reliable ultra-high performance liquid chromatography coupled with tandem mass spectrometry(UHPLC-MS/MS) method for the simultaneous deter...The present study was designed to develop and validate a rapid, sensitive, and reliable ultra-high performance liquid chromatography coupled with tandem mass spectrometry(UHPLC-MS/MS) method for the simultaneous determination of five major active constituents in the traditional Chinese medicinal preparation Xingxiong injection(XXI) in rat plasma, including quercetin 3-O-rutinoside(QCR), kaempferol 3-O-rutinoside(KFR), isorhamnetin 3-O-rutinoside(ISR), bilobalide(BB), and ligustrazine(LGT). The plasma samples were pretreated by protein precipitation with acetonitrile. The chromatographic separation was achieved on a Waters Symmetry C18 analytical column(2.1 mm × 100 mm, 3.5 mm) with a mobile phase of 0.1% aqueous formic acid(A)-acetonitrile(B). Quantitation of the five bioactive constituents was achieved. Naringin was used as the internal standard(IS). All the calibration curves showed good linearity(r > 0.996) over the concentration range, with the lowest limit of quantification(LLOQ) between 2-18 ng·m L^(-1). The intraand inter-day accuracy and precision of the analytes were both within acceptable limits. Moreover, satisfactory extraction recoveries(90.92%-104.03%) were obtained by protein precipitation. The validated method was successfully applied to a pharmacokinetic study of XXI in rats after intravenous administration at three doses. The pharmacokinetic parameters of the five compounds varied in a dose-dependent manner within the tested dosage range. The present study was the first report of pharmacokinetic study for XXI.展开更多
Astilbin is a potential immunosuppressive agent with minor cytotoxicity. Its oral bioavailability is supposed to be rather low and therefore a sensitive analytical method is required for its pharmacokinetic study afte...Astilbin is a potential immunosuppressive agent with minor cytotoxicity. Its oral bioavailability is supposed to be rather low and therefore a sensitive analytical method is required for its pharmacokinetic study after oral administration. A simple, sensitive and rapid liquid chromatography-tandem mass spectrometry(LC-MS/MS) method was developed and validated for the determination of astilbin in rat plasma. Plasma samples were subjected to liquid-liquid extraction with ethyl acetate and separated by reversed phase high performance liquid chromatography(HPLC) with methanol-0.01%(volume fraction) formic acid(50:50, volume ratio) as mobile phase. Quantitive determination was achieved on negative LC-MS/MS by a multiple reaction moitoring method with transitions m/z 449.1→150.9(quantifier) and m/z 449.1→284.9(qualifier) for astilbin and m/z 128.9→42.0 for internal standard(IS). A lower limit of quantification(LLOQ) of ng/mL was achieved within a short cycle time of 3.4 min. The method was successfully applied to a pharmacokinetic study involving oral and intravenous administrations of 6 mg/kg astilbin to six rats.展开更多
基金support of the Project of Science and Technology Agency of Gansu (No.1208RTZA211) and Lanzhou(Nos. 2012-2-67 and 2013-4-75)
文摘An electrochemical method based on a directly electrochemically reduced graphene oxide (ERGO) film coated on a glassy carbon electrode (GCE) was developed for the rapid and convenient determination of rutin in plasma. ERGO was modified on the surface of GCE by one-step electro-deposition method. Electrochemical behavior of rutin on ERGO/GCE indicated that rutin underwent a surface-controlled quasi-reversible process and the electrochemical parameters such as charge transfer coefficient (α), electron transfer number (n) and electrode reaction standard rate constant (ks) were 0.53, 2 and 3.4 s -1, respectively. The electrochemical sensor for rutin in plasma provided a wide linear response range of 4.70 × 10 ^-7 1.25 × 10^-5 M with the detection limit (s/n=3) of 1.84 × 10^-8 M. The assay was success- fully used to the pharmacokinetic study of rutin. The pharmacokinetic parameters such as elimination rate half-life (t1/2), area under curve (AUC), and plasma clearance (CL) were calculated to be 3.345 ± 0.647 rain, 5750 ±656.0 μg min/mL, and 5.891± 0.458 mL/min/kg, respectively. The proposed method utilized a small sample volume of 10 μL and had no complicated sample pretreatment (without deproteinization), which was simple, eco-friendly, and time- and cost-efficient for rutin pharmacokinetic studies.
文摘Three extraction methods were compared for their efficiency to analyze sitagliptin and simvastatin in rat plasma by LC-MS/MS, including (1) liquid-liquid extraction (LLE), (2) solid phase extraction (SPE) and (3) supported liquid extraction (SLE). Comparison of recoveries of analytes with different extraction methods revealed that SLE was the best extraction method. The detection was facilitated with ion trap-mass spectrometer by multiple reactions monitoring (MRM) in a positive ion mode with ESI. The transitions monitored were m./z 441.1→325.2 for simvastatin, 408.2→235.1 for sitagliptin and 278.1→260.1 for the IS. The lower limit of quantification (LLOQ) was 0.2 ng/mL for sitagliptin and 0.1 ng/mL for simvastatin. The effective SLE offers enhanced chromatographic selectivity, thus facilitating the potential utility of the method for routine analysis of biological samples along with pharmacokinetic studies.
文摘A novel bioanalytical method was developed and validated for the quantitative determination of darunavir(DRV) in rat plasma by employing hydrophilic interaction chromatography and tandem mass spectrometry(HILIC-MS/MS) with supported liquid extraction(SLE).lrbesartan(IRB) was used as an internal standard(IS).The analyte in rat plasma(200 μL) was isolated through SLE using ethyl acetate as the eluting solvent.The chromatographic separation was achieved on Luna-HILIC(250 mm × 4.6 mm,5 μm)column with a mobile phase of 0.1% of formic acid in water:acetonitrile(5:95,v/v),at a constant flow rate of 1.0mL/min.The MS/MS ion transitions for DRV(548.1→392.0) and IS(429.2→207.1) were monitored on an ion trap mass spectrometer,operating in the multiple reaction monitoring(MRM) mode.The lower limit of quantitation(LLOQ) was 0.2 ng/mL and quantitation range was 0.2-5000 ng/mL.The method was validated for its selectivity,sensitivity,carryover,linearity,precision,accuracy,recovery,matrix effect and stability.The method was successfully applied to pharmacokinetic study in rats.
文摘Poliumoside is the main active constituent of Callicarpa kwangtungensis Chun (CK), a traditional Chinese medicine for management of hemostasis. In this study, a rapid and selective ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC/ Q-TOF-MS) method was developed and validated to quantify poliumoside in rat plasma. The targeted analytes in rat plasma were prepared through protein-precipitation method using 10% trichloroacetic acid (TCA). The chromatographic separation was performed on a Waters BEH C<sub>18</sub> column (2.1 × 100 mm, 1.7 μm) by acetonitrile-water containing 0.1% formic acid. The calibration curve was linear over the range of 50 - 10,000 ng/mL (r<sup>2</sup> > 0.99). The intra-day or inter-day precision was less than 7.97% and accuracy was within ?7.00% - 3.36%. The developed method was successfully applied to pharmacokinetic study of poliumoside in rat plasma. Although being rapidly absorbed (T<sub>max</sub> ≤ 30 min), poliumoside was poorly bioavailable after oral administration (the absolute bioavailability was only 0.69%).
文摘Management of cardiovascular risk factors in diabetes demands special attention due to their co-existence. Pioglitazone (PIO) and telmisartan (TLM) combination can be beneficial in effective control of cardiovascular complication in diabetes. In this research, we developed and validated a high throughput LC-MS/MS method for simultaneous quantitation of PIO and TLM in rat plasma. This developed method is more sensitive and can quantitate the analytes in relatively shorter period of time compared to the previously reported methods for their individual quantification. Moreover, till date, there is no bioanalytical method available to simultaneously quantitate PIO and TLM in a single run. The method was validated according to the USFDA guidelines for bioanalytical method validation. A linear response of the analytes was observed over the range of 0.005-10 pg/mL with satisfactory precision and accuracy. Accuracy at four quality control levels was within 94.27%-106.10%. The inlxa- and inter-day precision ranged from 2.32% to 10.14% and 5.02% to 8.12%, respectively. The method was reproducible and sensitive enough to quantitate PIO and TLM in rat plasma samples of a preclinical pharmacokinetic study. Due to the potential of PIO-TLM combination to be therapeutically explored, this method is expected to have significant usefulness in future.
基金Mr.Thippani Ramesh thanks MHRD,Government of India for providing financial assistance
文摘A novel isocratic reverse phase high performance liquid chromatography (RP-HPLC) with photo diode array (PDA) detection method for the determination of dobutamine (DBT) in rat plasma was developed and validated after optimization of various chromatographic conditions and other experimental parameters. Homoveratrylamiue was used as an internal standard. Methanol was used as the extracting solvent for the preparation of plasma samples. Samples were separated on a Symmetry C18 (250ram x4.6mm i.d., 5 pro) analytical column. Acetonitrile and 15raM potassium dihydrogen phosphate (pH 5.0 with 0.3% TEA) (20:80, v/v) was used. The column oven temperature was optimized at 35 ~C and the flow rate was 0.8 mL/min. The detection wavelength was fixed at 230 nm for entire analysis. The calibration curve was found to be linear over the concentration range of 50-2000 ng/mL (ra=0.9992). The limit of quantification (LOQ) of the method was 50 ng/mL. The % RSD values of accuracy and precision values for intra and inter days were 〈 15% at quality control (QC) concentrations. Recovery, stability and robustness were studied within the acceptable range according to ICH guidelines. The method was efficiently applied to a pharmacokinetic study in healthy Wistar rats.
基金supported by the National Scientifc Foundation of China(NSFC nos.9081710330973672 and 20775055)+2 种基金Doctoral Fund of Ministry of Education of China(No 20110141110024)Hubei Provincial Scientifc Foundation(No 2011CDB475)the Fundamental Research Funds for the Central Universities
文摘A simple, sensitive and selective method of high-performance liquid chromatography (HPLC) has been successfully developed for separation of bavachinin enantiomers in Fructus Psoraleae and rat plasma. The separation and detection conditions of HPLC were optimized. Chiral bavachinin were separated with the mobile phase of methanol and water (70:30, v/v) at a flow rate of 1.0 mL/min. The linear ranges were in the range of 20-1000 μg/mL. The detection limits were tested as 4 ng/mL and 6 ng/mL for (+)-bavachinin and (-)-bavachinin, respectively. The method has been applied to analyze chiral bavachinin in rat plasma. HPLC-MS method was used to test the accuracy.
基金supported in part by a grant of the Scientific Research Program of Hainan Province (ZDYF2016143), China
文摘A simple, rapid and sensitive method based on an ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) has been developed and validated for the determination of pimavanserin in rat plasma. The analyte was extracted by protein precipitation with methanol and separated on an ACQUITY BEH C18 column (100 mm × 2.1 mm, 1.7μm; Waters, USA), with an isocratic elution of acetonitrile-water containing 10 mM ammonium acetate (70:30, v/v), at a flow rate of 0.2 mL/min for 2.5 rain. The analyte and clarithromyein (the internal standard) were detected and quantified in positive ion mode using multiple reaction monitoring transitions at m/z 428.2 - 223.0 for pimavanserin and m/z 748.5 - 589.5 for clarithromycin. Relative coefficient (r) for the calibration curve was more than 0.9980. The intra-day and inter-day precisions (relative standard deviation, RSD%) were less than 13.3% and 10.5%, respectively, and the accuracy (relative error, RE%) was within ± 11.5%. The analytical method was successfully applied to a routine pharmacokinetic study of pimavanserin in rats after oral administration at the dose of 10 mg/kg.
文摘Deoxyglycychloxazol (TY501) is a glycyrrhetinic acid derivative which exhibits high anti-inflammatory activity and reduced pseudoaldosteronism compared to glycyrrhetinic acid. In this study, a sensitive and rapid liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was established for the quantitation of TY501 in rat plasma. Plasma samples were treated by precipitating protein with methanol and supernatants were separated by a Symmetry C8 column with the mobile phase consisting of methanol and 10 mM ammonium formate (containing 0.1% of formic acid) (90:10, v/v). The selected reaction monitoring (SRM) transitions were performed at m/z 647.4→191.2 for TY501 and m/z 473.3→143.3 for astragaloside aglycone (IS) in the positive ion mode with atmospheric pressure chemical ionization (APCI) source. Calibration curve was linear over the concentration range of 5-5000 ng/mL. The lower limit of quantification was 5 ng/mL. The mean recovery was over 88%. The intra- and inter-day precisions were lower than 6.0% and 12.8%, respectively, and the accuracy was within ± 1.3%. TY501 was stable under usual storage conditions and handling procedure. The validated method has been successfully applied to a pharmacokinetic study after oral administration of TY501 to rats at a dosage of 10 mg/kg.
文摘A high performance liquid chromatographic method was developed and validated for the quantitative determination of catechin in rat plasma and its pharmacokinetic study after intragastric administration of Catechu and Xiongdanjiangre Wan into SD rats. Plasma samples were prepared by protein precipitation using methanol-5% aqueous zinc sulfate (70:30, v/v) as precipitant. Chromatographic separation was achieved on Hypersil Cl8 column (250 mm~ 4.6 mm, 10 pm) with acetonitrile-water-triethylamine (6:94:0.3, v/v/v, pH 4.0+0.1, adjusted with phos- phoric acid) as mobile phase, followed by a UV detection at 207 nm. Good linearity was obtained over the range of 0.143-7.15 mg/L of catechin, with correlation coefficient of 0.9992. The method was simple, sensitive, accurate and reproducible and' has been successfully applied to the pharmacokinetic study of catechin in rat plasma.
基金supported by Chongqing Municipal Engineering Technology Research Center Construction Project(No.CSTC2012PT-GC0003)Research Fund for Young Scholars of Xinan Hospital(No.SWH2013QN04)
文摘Neomangiferin, a natural C-glucosyl xanthone, has recently received a great deal of attention due to its multiple biological activities. In this study, a rapid and sensitive ultra-high performance liquid chromatography tandem mass spectrometry(UHPLC–MS/MS) method for the quantification of neomangiferin in rat plasma was developed. Using chloramphenicol as an internal standard(IS), plasma samples were subjected to a direct protein precipitation process using methanol(containing 0.05% formic acid). Quantification was performed by multiple reactions monitoring(MRM) method, with the transitions of the parent ions to the product ions of m/z 583.1-330.9 for NG and m/z 321.1-151.9 for IS. The assay was shown to be linear over the range of 0.2–400 ng/m L, with a lower limit of quantification of 0.2 ng/m L. Mean recovery of neomangiferin in plasma was in the range of 97.76%–101.94%. Relative standard deviations(RSDs) of intra-day and inter-day precision were both o 10%. The accuracy of the method ranged from94.20% to 108.72%. This method was successfully applied to pharmacokinetic study of neomangiferin after intravenous(2 mg/kg) and intragastric(10 mg/kg) administration for the first time. The oral absolute bioavailability of neomangiferin was estimated to be 0.53% 7 0.08% with an elimination half-life(t_(1/2)) value of 2.747 0.92 h, indicating its poor absorption and/or strong metabolism in vivo.
基金supported by the Natural Science Foundation of Liaoning Province,People’s Republic of China(NO.201510756-301)
文摘A rapid, simple and sensitive ultra-high performance liquid chromatography–tandem mass spectrometric(UPLC–MS/MS) method was developed and validated for the determination of hederasaponin B, an active triterpenoid saponin widely existed in Hedera helix L. Plasma samples were processed by protein precipitation with acetonitrile and separated on a Thermo Hypersil GOLD C18(2.1 mm × 50 mm,1.9 μm) at flow rate of 0.3 ml/min, with a gradient elution consisting of acetonitrile and water containing 0.1%(v/v) formic acid at 30 ℃ and detected by electrospray ionization mass spectrometry in the positive multiple reaction monitoring(MRM) mode. The linearity was found to be within the concentration range of 0.5–5000 ng/ml with a lower limit of quantification of 0.5 ng/ml. The absolute oral bioavailability of hederasaponin B was 0.24 ± 0.49%. This indicated that the concentration-time course of the hederasaponin B existed a double-peak phenomenon. This method was further applied to the determination of hederasaponin B in rat plasma and showed good practicability, for the first time, after intragastric(25 mg/kg) and intravenous(2 mg/kg) administration in rats.
文摘Context: Broussonetia papyrifera (L.) Vent. (Moraceae), a traditional Chinese medicinal herb, has been extensively applied for many years to treat various diseases. Its fruits (Fructus Broussonetiae) have been commonly used as an important tonic for the treatment of age-related disorders with long history;recent research has proved that it contains 32% to 35% fixed oils. The fixed oil is composed mainly of unsaturated fatty acids, including linoleic acid, methyl palmitate, oleic acid and linoleic acid ester. Objective: To investigate the chemistry of the fatty oil from Fructus Broussonetiae (FOFB) and its effects on plasma lipids. Methods: The chemical composition of FOFB was examined and identified by GC-MS. Thirty male Wistar rats fed diet containing FOFB and cholesterol were studied for 28 days. The effect of dietary FOFB on plasma lipids and adipose tissue was tested. Results: Twelve compounds of FOFB were examined and identified, the major components of fatty oil, 8,11-octadecadienoic acid (83.75%), palmitic acid (10.22%), octadecadienoic acid (2.97%) and 9-octadecenoic acid (1.69%) were found. FOFB significantly exhibited the activities of decreasing the rat adipose tissue weight, triacylglycerol, total cholesterol, and low-density lipoprotein cholesterol (LDL-C) concentrations while the rat body weight remained unchanged. Discussion: FOFB contained a large amount of PUFA which had the effect on reducing plasma lipids and adipose.
基金supported by the National Natural Science Foundation of China(No.81073030)the National Key Technology R&D Program in the 11th Five Year Plan of China(No.2008BA151B00-2)
文摘AIMS: To develop an HPLC-MS/MS method for the quantification of platycodin D(PD) in rat plasma, and to acquire the main pharmacokinetic parameters of PD after oral administration of pure PD or of Platycodi Radix extract(PRE) containing PD. METHOD: Plasma samples were pretreated with solid-phase extraction using an Oasis HLB SPE cartridge. Madecassoside was used as the internal standard(IS). Chromatographic separation was achieved on an ODS column(100 mm × 2.1 mm i.d., 3.5 μm) with a mobile phase consisting of acetonitrile/water(30 : 70, V/V) containing 0.1 mmol L 1ammonium acetate at a flow rate of 0.25 mL min 1. The detection was performed on a triple quadruple tandem mass spectrometer using an electrospray ionization(ESI) source with a chromatographic run time of 3.0 min. The detection was operated by multiple reaction monitoring(MRM) of the transitions of m/z 1 223.6→469.2 for PD and of m/z 973.6→469.2 for madecassoside(IS), respectively. RESULTS: The calibration curve was linear from 5 to 2 000 ng mL 1(r2>0.99) with a lower limit of quantification(LLOQ) of 5 ng mL 1. The intra- and inter-day precision(relative standard deviation, RSD) values were below 15% and the accuracy(relative error, RE) was from 15% to +15% at three quality control(QC) levels. Plasma concentrations of PD were determined for 24 h after i.v. administration of PD, and oral administration of PD and PRE, respectively. The absolute oral bioavailability of PD in rats was found to be(0.48 ± 0.19)% when administered PD, and to be(1.81 ± 0.89)% when administered PRE. CONCLUSION: The developed HPLC-MS/MS method was successfully applied to assess the pharmacokinetic parameters and oral bioavailability of PD in rats after administration of PD and Platycodi Radix extract.
基金supported by the National Mega-Project for Innovative Drugs (Nos. 2012ZX09301002 and 2014ZX09507009)the National Natural Science Foundation of China, China (Nos. 81321004 and 81361138020)
文摘(E)-Methyl-4-aryl-4-oxabut-2-enoate(YH-8) is a novel PKn B protein kinase inhibitor with good anti-tuberculosis activity. To evaluate its pharmacokinetics in rats, a sensitive and selective high performance liquid chromatography–tandem mass spectrometric(LC–MS/MS) method has been developed and validated for the quantification of YH-8 in rat plasma for the first time. Samples were pre-treated using a liquid–liquid extraction with ethyl acetate and the chromatographic separation was performed on a C18 column by gradient elution with methanol–water as the mobile phase. YH-8 was detected using a tandem mass spectrometer in positive selected reaction monitoring(SRM) mode. Method validation revealed good linearity over the range of1–500 ng/m L for YH-8 with a lower limit of quantification(LLOQ) of 1 ng/m L. Intra- and inter-day precision of YH-8 assay in rat plasma samples were 2.0%–6.8%, with accuracy of the method being 100.69%–106.18%.Stability test showed that when spiked into rat plasma, YH-8 was stable for 12 h at room temperature, for up to15 days at -70℃, and after three freeze-thaw cycles. Extracted samples were found to be stable over 12 h in an auto-sampler. The method was successfully applied to the pharmacokinetic study of YH-8 in rats after oral administration at 100 mg/kg and 200 mg/kg.
基金supported by the National Natural Science Foundation of China(No.81073009)a Project Fund from The Priority Academic Program Development of Jiangsu Higher Education Institutions.
文摘Assays based on high-performance liquid chromatography(HPLC)and liquid chromatography tandem mass spectrometry(LC–MSn)have been developed and validated for the determination and metabolite identification of the bidesmosidic triterpenoid saponin,BTS-1(3-O-β-D-galactopyranosyl-(1-2)-[β-D-xylopyranosyl-(1-3)]-β-D-glucuronopyranosyl gypsogenin 28-O-α-L-arabinopyranosyl-(1-3)-βD-xylopyranosyl-(1-4)-α-L-rhamnopyranosyl-(1-2)-β-D-fucopyranoside),in rat plasma.The assay was successfully applied to a pharmacokinetic study in rats given a single oral dose of BTS-1(400 mg/kg).The results indicated that the compound was rapidly absorbed(Tmax=1.2870.29 h,Cmax=37.475.6 mg/mL)and slowly eliminated(t1/2=13.276.6 h).In addition,secondary glycosides and aglycones of BTS-1 were detected and identified.Since these metabolites are known to be activeα-glucosidase inhibitors,they probably play an important role in mediating the pharmacological effects of the saponin.
基金financially supported by National Natural Science Foundation of China/81973439Heilongjiang University of Chinese Medicine Research Fund/201504+4 种基金National Natural Science Foundation of China/81803686Research Fund of Heilongjiang University of Traditional Chinese Medicine/201504Heilongjiang Postdoctoral Research Start-up Funding Project/LBH-Q16214Heilongjiang Science Foundation Project/H2018056Heilongjiang University of Traditional Medicine Talents Support Plan/2018RCD03。
文摘Objective:The objective of the study was to develop a rapid and sensitive ultra-performance liquid chromatography-tandem mass spectrometric method for the determination of tetrandrine,fangchinoline,and cyclanoline in rat plasma and to investigate their pharmacokinetics after oral administration of Stephaniae Tetrandrae Radix extracts.Methods:Sample pretreatment involved methanol pretreatment and liquid–liquid extraction of ethyl acetate from plasma with methanol.Tramadol was used as the internal standard.The analysis was performed using an high strength silica T3 column(100 mm×2.1 mm,1.8μm)and a gradient elution method consisting of mobile phase solution A(0.1%formic acid in water)and B(acetonitrile)at a flow rate of 0.4 mL/min.The detection was performed using a triple quadrupole tandem mass spectrometer in the multiple reaction monitoring mode and using an electrospray ionization source in the positive ionization mode.Results:High efficiency was achieved with an analysis time of 4 min/sample.The calibration curve linear in the concentration range of 1250 ng/ml(R^(2)≥0.9900)and the lower limit of quantification is 1 ng/ml.The intraday and interday precision(relative standard deviation)values were lower than 9.4.Accuracy(relative error)was within 10.3%at all three quality control levels.Conclusions:This method was successfully applied in pharmacokinetics of tetrandrine,fangchinoline,and cyclanoline in rats after oral administration of Stephaniae Tetrandrae Radix extracts.The maximum plasma concentration(C_(max))of tetrandrine,fangchinoline,and cyclanoline was 124.71±16.08,84.56±3.28,and 57.61±6.26 ng/mL,respectively.The time to reach C_(max)was 10.39±3.04 for tetrandrine,10.17±3.04 for fangchinoline,and 6.40±3.16 for cyclanoline.The pharmacokinetic results might help further guide the clinical application of Stephaniae Tetrandrae Radix.
文摘<p> <strong>Short Retraction Notice</strong> </p> <p> The paper does not meet the standards of "American Journal of Analytical Chemistry". The article has been retracted due to the conflicts of interests between all authors to straighten the academic record. Aim is to promote the circulation of scientific research by offering an ideal research publication platform with due consideration of internationally accepted standards on publication ethics. The Editorial Board would like to extend its sincere apologies for any inconvenience this retraction may have caused. The full retraction notice in PDF is preceding the original paper, which is marked "RETRACTED". </p>
基金financially supported from National Natural Science Foundation of China(Nos.81673569,and 81473343)Program for New Century Excellent Talents in University(No.NECT-13-1034)a Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions
文摘The present study was designed to develop and validate a rapid, sensitive, and reliable ultra-high performance liquid chromatography coupled with tandem mass spectrometry(UHPLC-MS/MS) method for the simultaneous determination of five major active constituents in the traditional Chinese medicinal preparation Xingxiong injection(XXI) in rat plasma, including quercetin 3-O-rutinoside(QCR), kaempferol 3-O-rutinoside(KFR), isorhamnetin 3-O-rutinoside(ISR), bilobalide(BB), and ligustrazine(LGT). The plasma samples were pretreated by protein precipitation with acetonitrile. The chromatographic separation was achieved on a Waters Symmetry C18 analytical column(2.1 mm × 100 mm, 3.5 mm) with a mobile phase of 0.1% aqueous formic acid(A)-acetonitrile(B). Quantitation of the five bioactive constituents was achieved. Naringin was used as the internal standard(IS). All the calibration curves showed good linearity(r > 0.996) over the concentration range, with the lowest limit of quantification(LLOQ) between 2-18 ng·m L^(-1). The intraand inter-day accuracy and precision of the analytes were both within acceptable limits. Moreover, satisfactory extraction recoveries(90.92%-104.03%) were obtained by protein precipitation. The validated method was successfully applied to a pharmacokinetic study of XXI in rats after intravenous administration at three doses. The pharmacokinetic parameters of the five compounds varied in a dose-dependent manner within the tested dosage range. The present study was the first report of pharmacokinetic study for XXI.
基金the National Natural Science Foundation of China,the Science and Technology Major Specialized Projects for "Significant New Drugs Creation" of the 12th Five-year Plan of China,the National Key Technology R&D Program of the Ministry of Science and Technology,China
文摘Astilbin is a potential immunosuppressive agent with minor cytotoxicity. Its oral bioavailability is supposed to be rather low and therefore a sensitive analytical method is required for its pharmacokinetic study after oral administration. A simple, sensitive and rapid liquid chromatography-tandem mass spectrometry(LC-MS/MS) method was developed and validated for the determination of astilbin in rat plasma. Plasma samples were subjected to liquid-liquid extraction with ethyl acetate and separated by reversed phase high performance liquid chromatography(HPLC) with methanol-0.01%(volume fraction) formic acid(50:50, volume ratio) as mobile phase. Quantitive determination was achieved on negative LC-MS/MS by a multiple reaction moitoring method with transitions m/z 449.1→150.9(quantifier) and m/z 449.1→284.9(qualifier) for astilbin and m/z 128.9→42.0 for internal standard(IS). A lower limit of quantification(LLOQ) of ng/mL was achieved within a short cycle time of 3.4 min. The method was successfully applied to a pharmacokinetic study involving oral and intravenous administrations of 6 mg/kg astilbin to six rats.