RETRACTED: Validated UPLC-MS/MS Method for the Simultaneous Quantification of Vortioxetine and Fluoxetine in Plasma: Application to Their Pharmacokinetic Interaction Study in Wistar Rats

Short Retraction Notice 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 The article has been retracted due to the conflicts of interests between all authors to straighten the academic record.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".

LC-MS/MS determination and pharmacokinetic study of bergenin, the main bioactive component of Bergenia purpurascens after oral administration in rats

Bergenin, a C-glucoside of 4-O-methyl gallic acid from Bergenia purpurascens, is a naturally antitussive and expectorant agent. A rapid and sensitive liquid chromatography tandem mass spectrometry （LC-MS/MS） method has been developed and validated for the determination of the active component--bergenin, in rat plasma after oral administration of aqueous B. purpurascens extract. The plasma samples were pretreated by protein precipitation with acetonitrile and chromatographic separation was achieved on a Diamonsil C18 column （150mim×4.6mm, 5μm） with isocratic elution using a mobile phase consisting of water- methanol （30：70, v/v） at a flow rate of 0.6 mL/min. The detection was accomplished by a triple- quadrupole tandem mass spectrometer in multiple-reaction monitoring （MRM） scanning via an electrospray ionization （ESI） source operating in the negative mode. The optimized mass transition ion-pairs （m/z） for quantitation were 327.3/192.0 for bergenin, and 431.1/311.1 for IS. The time for each analysis run was only 3.5 min between injections. The calibration curve exhibited good linearity （r2〉 0.99） over a range of 1.00-2000 ng/mL for bergenin. The lower limit of quantitation （LLOQ） was 1.00ng/mL. The intra- and inter-day precisions were no more than 11.8%, and relative errors （RE） were within the range of 0.0-4.4%. The validated method was successfully applied to investigate the pharmacokinetics of bergenin after oral administration of B. purpurascens extract in rats.

Comparative pharmacokinetics of five saponins after intravenous administration of TSFS injection and TSFS injection plus TFFG in rats under different physiological states

Sanqi is a popular traditional Chinese medicine and commonly used for promoting blood circulation and removing blood stasis. Notoginsenoside R1, ginsenoside Rg1, Re, Rb1 and Rd are the major active constituents of Sanqi. The purpose of the study was to investigate the pharmacokinetic behavior of the five active constituents from total saponin from Sanqi when it was used in the blood stasis animals or in combination with Gegen. The concentrations of the five active constituents in rat plasma were determined by an ultra-HPLC-ESI-MS/MS method. The main pharmacokinetic parameters were calculated and statistically analyzed using the unpaired student＆#39;s t-test. It was found that the pharmacokinetic parameters of notoginsenoside R1, ginsenoside Rg1 and Rb1 represented a statistically significant difference （Po0.05） between the normal rats and the blood stasis rats after administration of total saponin from Sanqi （TSFS）. And there were statistically significant differences （Po0.05） in the pharmacokinetic parameters of all the five constituents between administration of TSFS alone and combined with total flavonoid from Gegen （TFFG） in blood stasis rats. It suggested that the pharmacokinetic behavior of the active constituents from TSFS could be changed when it was used in blood stasis animals or in combination with TFFG.

The pharmacokinetic study of rutin in rat plasma based on an electrochemically reduced graphene oxide modified sensor

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.

Comparison of conventional and supported liquid extraction methods for the determination of sitagliptin and simvastatin in rat plasma by LC-ESI-MS/MS

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.

Direct injection HILIC-MS/MS analysis of darunavir in rat plasma applying supported liquid extraction

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.

Validated UPLC/Q-TOF-MS Method for Determination of Poliumoside in Rat Plasma and Its Application to Pharmacokinetic Study

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 C18 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 (r2 > 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 (Tmax ≤ 30 min), poliumoside was poorly bioavailable after oral administration (the absolute bioavailability was only 0.69%).

Development and validation of a high throughput LC–MS/MS method for simultaneous quantitation of pioglitazone and telmisartan in rat plasma and its application to a pharmacokinetic study

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.

Optimization and validation of a fast RP-HPLC method for the determination of dobutamine in rat plasma:Pharmacokinetic studies in healthy rat subjects

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.

Chiral separation of bavachinin in Fructus Psoraleae and rat plasma by liquid chromatography using permethylated-b-CD as a chiral selector

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.

Development of a UPLC–MS/MS method for determination of pimavanserin tartrate in rat plasma: Application to a pharmacokinetic study

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.

Development of an LC–MS/MS method for the quantitation of deoxyglycychloxazol in rat plasma and its application in pharmacokinetic study

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.

Identification and characterization of chemical constituents in Mahuang Guizhi Decoction and their metabolites in rat plasma and brain by UPLC-Q-TOF/MS

Objective:Mahuang Guizhi Decoction(MGD),an essential herbal pair in traditional Chinese medicine,is able to release cold,fever and asthma,mainly containing alkaloids,flavonoids,phenylpropanoids and amino acids.However,the absorption and distribution of these four category compounds in vivo still remained unclearly.Methods:In our research,we utilized UPLC-Q-TOF-MS technique to identify the constituents within MGD,as well as the prototypes of MGD and their metabolites absorbed in plasma and brain.We further profiled the drug-time curve of prototypes and metabolites of MGD both in plasma and brain.Results:Our results showed that 105 constituents were characterized in MGD.Thirty of them could be absorbed into blood,and ten of them could be distributed into brain.We also discovered eight new bio-transformed metabolites in blood,and a half of which could pass through the blood–brain barrier.In addition,all components detected in vivo could be absorbed and distributed immediately.Conclusion:These findings provide an approachable method to analyze the potential bio-active compounds in MGD and their in vivo behaviors,which could promote the efficacious material basis study of MGD and the security of clinical utilization.

Development of a method for the quantitative determination of geniposide in rat plasma by liquid chromatography-tandem mass spectrometry with positive/negative ion-switching electrospray ionization and its application in a pharmacokinetic study in rats

Geniposide is a major bioactive constituent isolated from Gardeniajasminoides Ellis. To evaluate the pharmacokinetics of geniposide in pre-clinical studies, a rapid and specific liquid chromatography-tandem mass spectrometry （LC-MS/MS） method was developed and validated. After simple protein precipitation, geniposide was analyzed on a DiamonsilR C18 column with a mobile phase of 10 mM ammonium acetate and methanol （20：80, v/v） at a flow rate of 0.6 mL/min. Detection was performed in ＂Truncated＂ multiple-reaction monitoring （MRM） mode with positive electrospray ionization （ESI） at m/z 411→411 for geniposide, and MRM mode with negative ESI ionization at m/z 415→295 for puerarin （internal standard, IS）. Linearity was established in the concentration range from 10.0 to 5000 ng/mL. The extraction recoveries ranged from 84.8% to 90.5% at concentrations of 10.0, 500 and 4.5x 103 ng/mL. The lower limit of quantification （LLOQ） was 10.0 ng/mL with 50 ~tL plasma. The validated method was successfully applied to the pharmacokinetic study of geniposide in rats at a dose of 200 mg/kg by oral administration.

Quantitative determination of cyclophosphamide in rat plasma using an on-line SPE HPLC-DAD

A rapid and simple liquid chromatography method with on-line solid phase extraction was developed and validated for the quantitative determination of cyclophosphamide in rat plasma.The plasma sample was first extracted on an Acclaim？ Polar Advantage II C18 guard column（PA II C18,10 mm×4.6 mm,5 μm）,which was also the on-line Extraction Cartridge SPE column,by washing with 100% H2O for 1 min.The extracted sample was then eluted onto a PA II C18 column（150 mm×4.6 mm,5 μm） and separated by isocratic elution with acetonitrile-water（40：60,v/v）.The mobile phase was run at a flow rate of 1.0 mL/min,and the UV detector was set at 195 nm.Retention time of cyclophosphamide was 4.3 min and the total run-time was 6 min.The linear range of the standard curve was from 1.0 to 200 μg/mL（r2 = 0.9999）,and the limits of quantification and detection were 1.0 μg/mL（RSD10%,n = 5） and 0.3 μg/mL（RSD13%,n = 5）,respectively.Both intra-and inter-day variations were less than 5.6%.The developed method can be used for the therapeutic drug monitoring of cyclophosphamide in the clinic.

Development and validation of an RP-HPLC-UV method for the determination of daphnoretin in rat plasma

A sensitive RP-HPLC-UV method has been developed and validated for the quantification of daphnoretin in rat plasma. Daphnoretin was extracted from rat plasma by protein precipitation and liquid-liquid extraction. Separation was performed on a Diamonsil C18 column （200 mm× 4.6 mm, 5 μm） with a mobile phase of methanol-20 mmol/L ammonium acetate （adjusted to pH 3.2 with acetic acid, 42：58, v/v） at a flow rate of 1.0 mL/min. The UV detector was set at 345 nm and column temperature was set at 40 ℃. The calibration curves were linear over the concentration range of 0.020-2.00 ~tg/mL, The lower limit of quantification （LLOQ） of daphnoretin in rat plasma was 0.020 μg/mL. The intra- and inter-day relative standard deviation （RSD） for measurement of quality control （QC） samples （0.050, 0.200 and 1.60 μg/mL） ranged from 5.0%-10.6%. Relative error （RE） was from ±（1.2%-2.5%）. The validated method was used successfully in a pharmacokinetic study of daphnoretin in rats after intraperitoneal injection.

A high performance liquid chromatography method for the quantitative determination assay of sitagliptin in rat plasma and its application in pharmacokinetics study

A new high-performance liquid chromatography （HPLC） method for the quantitative determination of sitagliptin in rat plasma was developed and validated for pharmacokinetics study. The plasma was spiked with the internal standard （hydrocortisone, IS）, treated with sodium hydroxide, and extracted with ethyl acetate. The extracted analyte was injected into an Agilent Zorbax Extend-C18 column （250 mm×4.6 mm, 4 μm） maintained at 30℃ and monitored at 267 nm. The mobile phase consisting of methanol-water （60：40, v/v, containing 10 mM Tris and 10 mM triethylamine） was titrated to pH 9.0 using 1 mol/L hydrochloric acid. The flow rate was 1.0 mL/min. The method showed high specificity. Calibration curves of the peak area ratio of each analyte/IS versus sitagliptin concentration were linear in the range of 0.75-100.0μg/mL （r〉0.9957）. The lower limit of quantification （LLOQ） was 0.75 μg/mL. The intra-day and inter-day coefficient of variation was lower than 10%. The accuracy （relative recovery） at three levels was 105.3% （0.75 μg/mL）, 99.8% （10.0 μg/mL） and 99.0% （100.0 μg/mL）. The extraction recovery was 81.5%, 82.4% and 84.5% at the concentrations of 0.75, 10.0 and 100.0 μg/mL, respectively. The short-term, long-term, freeze-thaw storage stability of plasma samples and the stability of standard solutions were satisfactory. This HPLC method is suitable for determining the concentration of sitagliptin in rat plasma and it was applied to determine the concentration-time profiles of sitagliptin in rat plasma following oral administration of sitagliptin.

Quantitative determination of ganoderic acid T in rat plasma by a sensitive RP-HPLC method and its application in pharmacokinetic studies

A selective and sensitive HPLC method has been developed and validated for the quantification of ganoderic acid T in rat plasma. A reverse-phase column was used with UV detection at 245 nm. The mobile phase consisted of methanol-water-acetic acid （95.5：4.5：0.5, v/v/v） run at a flow rate of 1 mL/min. Testosterone propionate was used as the internal standard. The standard curve was linear over the range of 0.05-50 ~tg/mL in rat plasma with a linear correlation coefficient greater than 0.999. The lower limit of quantification of this assay was 20 ng/mL. The recoveries of samples at 0.05, 2 and 40 μg/mL were 97.6%, 98.4% and 103.2%, respectively. The relative standard deviations of intra- and inter-day assay variations were less than 8.2%. The usefulness of the assay was confirmed by the successful analysis of plasma samples from a pharmacokinetics study in rats. Following a single dose of ganoderic acid T （5 mg/kg for i.v. or 14 mg/kg for p.o.）, the main pharmacokinetic parameters by intravenous injection were： t1/2α （5.46±1.25） min; t1/2β：（227.18±11.40） min; CL： （1.09±0.16） mL/（kg·min）; A UC0-12 h： （3939.13±311.14） μg.min/mL; AUC0-12h （4681.96±710.70）μg.min/mL and the absolute bioavailability was 41.98%±2.40%. This method is simple, sensitive, and accurate. It is suitable for pharmacokinetic studies of ganoderic acid in rats.

Determination of metformin in diabetic rat plasma by an improved ion-pair high-performance liquid chromatography: application to a pharmacokinetic study

An efficient and sensitive ion-pair HPLC-UV method using atenolol as internal standard （IS） was developed and validated for the determination of metformin in the plasma of diabetic rats. Plasma samples were deproteinated with 10% （v/v） perchloric acid. Separation was achieved on a UltimateTM AQ-C18 column （250 mm×4.6 mm, 5 μm） with a mobile phase （pH 5.05） composed of acetonitrile-water （31：69, v/v, containing 0.002 M sodium dodecyl sulfate, 0.0125 M potassium dihydrogen phosphate, 0.015 M triethylamine） at a flow rate of 1.0 mL/min. The calibration curve was linear （r〉0.994） between 7.5 and 4000 ng/mL. The lower limit of quantification （LLOQ） was 7.5 ng/mL. The precision was validated and the relative standard deviation was in the range of 1.87% to 15.70%; the accuracy was between 93.98%-106.89%. The mean recoveries were 95.40% and 95.31% for metformin and IS, respectively. The relative error （RE） of stability at different storage conditions was within ±9.00%. This method was used to determine the concentration-time profile of metformin in diabetic rat plasma following an oral administration of metformin at the dose of 10 mg/kg. Our results indicated that ion-pair HPLC-UV method using UltimateTM AQ-C18 column was effective for the pharmacokinetic studies of high polarity compounds like metformin.

An HPLC-MS/MS method for the quantitative determination of platy-codin D in rat plasma and its application to the pharmacokinetics of Platycodi Radix extract

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.