Stereoselective pharmacokinetics of tetrahydropalmatine after oral administration of (-)-enantiomer and the racemate

Tetrahydropalmatine (THP) is a biologically active ingredient isolated from a traditional Chinese herb Rhizoma corydalis (yanhusuo). THP is a racemic mixture which contains 50% of the (+) and 50% of (-) enantiomer. The (-) enantiomer accounts for most of the analgesic effects. Plasma concentrations of THP enantiomers were analyzed by chiral high-performance liquid chromatography (HPLC) on a Chiralcel OJ column with quantification by UV at 230 nm. The method was used to determine the pharmacokinetics of THP enantiomers in rats and dogs after oral administration of rac-THP or (-)-THP. The pharmacokinetic profiles of the two enantiomers after dosing with rac-THP were significantly different both in rats and dogs. The mean C(max) and AUC(0-infinity) values in rats were 1.93 +/- 0.36 microg/ml and 6.65 +/- 2.34 microg x h/ml for the (-) enantiomer, and 1.11 +/- 0.25 microg/ml and 2.03 +/- 0.45 microg x h/ml for the (+) enantiomer. The mean C(max) and AUC(0-infinity) in dogs were 1.60 +/- 0.81 microg/ml and 9.88 +/- 2.58 microg x h/ml for the (-) enantiomer, while 0.36 +/- 0.21 microg/ml and 1.22 +/- 0.40 microg x h/ml for the (+) enantiomer. rac-THP at 40 mg/kg and (-)-THP at 20 mg/kg had very similar plasma concentration-time profiles, and C(max), AUC(0-infinity), and t(1/2) of the (-) enantiomer in both rats and dogs, indicating that the two treatments were equivalent with respect to the pharmacokinetic properties of the (-) enantiomer.     

High performance liquid chromatographic determination of 1,2-[bis(1,2-benzisoselenazolone-3(2H)-ketone)]-ethane (BBSKE), a novel organoselenium compound, in dog plasma using pre-column derivatization and its application in pharmacokinetic study

A novel HPLC-UV method with pre-column derivatization by using 2-mercaptoethanol was established for determination of 1,2-[bis(1,2-benzisoselenazolone-3(2H)-ketone)]-ethane (BBSKE) in dog plasma. The derivatives were identified by mass spectrometry. The method had a good linear range of 0.05-2 microg/ml (r(2)=0.9995). The lower limit of quantification (LOQ) was 0.05 microg/ml. The precision and accuracy were less than 7%. After dosing of BBSKE (30 mg/kg, p.o. and 0.79 mg/kg, i.v.) in dogs, AUC(0-t) were 5.72+/-2.42 and 1.35+/-0.41 microg h/ml; t(1/2) were 4.6+/-2.1 and 1.7+/-0.6h, respectively. The method was successfully applied to the pharmacokinetic study in dogs.     

Amylin receptors mediate the anorectic action of salmon calcitonin (sCT)

The teleost salmon calcitonin (sCT), but not mammalian CT, shows similar biologic actions in the skeletal muscle as amylin and calcitonin gene-related peptide (CGRP). The peptides have also been shown to reduce food intake in rams. Because sCT, but not amylin, binds irreversibly to amylin binding sites, the aim of the present study was to compare the anorectic potency of both peptides. To determine whether sCT reduces food intake through interaction with amylin binding sites, we also tested whether appropriate antagonists (CORP 8-37, AC 187) attenuate the anorectic effect of sCT. Finally, we wanted to know whether rat calcitonin (rCT) and sCT reduce food intake to the same extent. Peptides were injected intraperitoneally at dark onset in 24 h food-deprived rats. At doses of 5 or 0.5 microg/kg, the anorectic effect of sCT was more potent and lasted much longer (e.g. 5 microg/kg: sCT > 10 h; amylin approx. 2 h) than that of amylin. Both CORP 8-37 and AC 187 (10 microg/kg) markedly reduced the anorectic action of sCT (0.5 microg/kg). In contrast to sCT, rCT (0.5 microg/kg) had no effect on food intake. It is concluded that sCT s anorectic effect is partly mediated by amylin receptors. Irreversible binding of sCT to amylin receptors may lead to a stronger and prolonged effect in comparison to amylin due to a sustained activation of the binding sites. Similar to other actions of CTs, the anorectic potency of sCT in rats was higher than that of mammalian (rat) CT. This agrees with binding profiles of amylin, sCT, and rCT at amylin binding sites as observed in in vitro studies.     

Determination of ginsenoside Rd in dog plasma by liquid chromatography-mass spectrometry after solid-phase extraction and its application in dog pharmacokinetics studies

A sensitive liquid chromatography-mass spectrometric (LC/MS) method for the quantification of ginsenoside Rd in dog plasma was developed and validated after solid-phase extraction (SPE).Chromatographic separation was achieved on a reversed-phase Cromosil C(18) column with the mobile phase of acetonitrile-ammonium chloride (500 micromol/L) and step gradient elution resulted in a total run time of about 5.5 min. The analytes were detected by using an electrospray negative ionization mass spectrometry in the selected ion monitoring (SIM) mode. A good linear relationship was obtained in the concentration range studied (0.005-2.500 microg/mL) (r=0.9998). Lower limit of quantification (LLOQ) was 5 ng/mL by using 500 microL plasma sample. Average recoveries ranged from 70.71 to 75.89% in plasma at the concentrations of 0.010, 0.100 and 2.500 microg/mL. Intra- and inter-day relative standard deviations were 8.49-11.71 and 5.71-16.48%, respectively. This method was successfully applied to the pharmacokinetic studies on dogs. The absolute bioavailability of Rd in dogs was 0.26%.     

Improved RP-HPLC method to determine neferine in dog plasma and its application to pharmacokinetics

Existing methods to determine neferine, a bisbenzylisoquinline alkaloid, either have no internal standard or lack selectivity, or take longer time. Here an improved reverse-phase high-performance liquid chromatographic (RP-HPLC) method was established in biological samples. The extraction recovery was 90.9% for neferine at concentration level of 0.2 microg/ml and 77.7% for dauricine (the internal standard) at 5 microg/ml in dog plasma, respectively. The linear quantification range of the method was 25-2000 ng/ml in dog plasma, with linear correlation coefficients greater than 0.999. The intra-day and inter-day relative standard deviations (R.S.D.s) for neferine at 50, 200 and 1000 ng/ml levels in dog plasma fell in the range of 3.0-5.4% and 4.3-9.5%, respectively. The RP-HPLC method was successfully applied to a pharmacokinetics study, in which experimental dogs received a single dose of neferine (5 mg/kg i.v. or 10 mg/kg p.o.). The pharmacokinetic result was presented.     

Bioanalysis and pharmacokinetics of the p38 MAPkinase inhibitor SB202190 in rats

We have developed a sensitive and reproducible high performance liquid chromatography (HPLC)-UV method for the quantification of the p38 MAPkinase inhibitor SB202190 in serum, kidney homogenates and urine samples. Liquid-liquid extraction of SB202190 from the samples was performed using diethylether after adding a derivative of SB202190 as internal standard (I.S.). Chromatography was carried out using a C8 reversed-phase column with an isocratic mobile phase consisting of acetonitrile-water-trifluoroacetic acid (30:70:0.1, v/v/v; pH 2.0). Both drug and I.S. were measured at 350 nm and eluted at 5.0 and 10.6 min, respectively. Peak-height ratios of the drug and the I.S. were used for the quantification of SB202190 from the different matrixes. The limit of quantitation of SB202190 in serum, kidney and urine were 0.25 microg/ml, 1 microg/g and 1 microg/ml, respectively. The average recoveries were 74, 75 and 92% in serum, kidney and urine, respectively. The intra- and inter-day precision (% CV) and accuracy (% bias) were below 15% for all concentrations. The method was successfully applied for a pharmacokinetic study of SB202190 in rats.     

Determination of schizandrin in rat plasma by high-performance liquid chromatography-mass spectrometry and its application in rat pharmacokinetic studies

A sensitive liquid chromatography-mass spectrometric (LC/MS) method for the quantification of schizandrin in rat plasma was developed and validated after solid-phase extraction (SPE). Chromatographic separation was achieved on a reversed-phase Shimadzu C(18) column with the mobile phase of acetonitrile-sodium acetate (10 micromol/L) and step gradient elution resulted in a total run time of about 11.7 min. The analytes were detected using an electrospray positive ionization mass spectrometry in the selected ion monitoring (SIM) mode. A good linear relationship was obtained in the concentration range studied (0.005-2.000 microg/mL) (r=0.9999). Lower limit of quantification (LLOQ) was 5 ng/mL and the lower limit of detection (LLOD) was 2 ng/mL using 100 microL plasma sample. Average recoveries ranged from 75.85 to 88.51% in plasma at the concentrations of 0.005, 0.100 and 1.000 microg/mL. Intra- and inter-day relative standard deviations were 5.95-12.93% and 3.87-14.53%, respectively. This method was successfully applied for the pharmacokinetic studies in rats.     

A capillary gas chromatography-selected ion monitoring mass spectrometry method for the analysis of atractylenolide I in rat plasma and tissues, and application in a pharmacokinetic study

The aim of this paper is to investigate the characteristics of atractylenolide I (AO-I) in the body by a GC-MS method. All bio-samples were cleared up with a liquid-liquid extraction procedure. The calibration curves were linear within a range of 5-1000 ng/mL for plasma samples, 0.06-16.00 microg/g for cerebellum samples, and 0.03-8.00 microg/g for other tissue samples. The limit of quantification (LOQ) for AO-I was 1.0 ng/mL or 1.0 ng/g (S/N>micro=10) in the bio-samples. In the applications, the main pharmacokinetic parameters were firstly obtained as follows: Tmax=0.37+/-0.19 h, Cmax=0.26+/-0.05 microg/mL, AUC=1.95+/-0.30 microgh/mL and ka=10.08+/-5.60 h(-1). The tissue distribution of AO-I in rats after the oral administration of 50.0mg/kg was from 0.225 to 0.031microg/g with a decreasing tendency in different tissues like liver>kidney>spleen>cerebellum>heart>cerebrum>lung. The protein binding in rat plasma, human plasma and bovine serum albumin was 80.8+/-3.9, 90.6+/-3.1 and 60.9+/-5.1%, respectively.     

Simultaneous determination of levomepromazine,midazolam and their major metabolites in human plasma by reversed-phase liquid chromatography

A sensitive and reliable high-performance liquid chromatographic (HPLC) assay is a prerequisite for pharmacokinetic analysis of continuous infusion of levomepromazine adjuvant to midazolam. We developed such a method to determine the levels of levomepromazine, midazolam and their major metabolites (levomepromazinesulfoxide, desmethyl-, didesmethyllevomepromazine, O-desmethyllevomepromazine and alpha-hydroxy-midazolam) simultaneously. Desmethylclomipramine was used as an internal standard (I.S.). The lower limit of quantification of this assay was set for levomepromazine 4.1 microg/l, levomepromazinesulfoxide 4.9 microg/l, O-desmethyllevomepromazine 18.4 microg/l, alpha-hydroxymidazolam 26.6 microg/l, midazolam 23.4 microg/l, didesmethyllevomepromazine 15.8 microg/l, and desmethyllevomepromazine 6.6 microg/l. The between- and within day assay variations were commonly below 5%. The recovery in human plasma for the different analytes varied between 85 and 11%. The accuracy of this assay varied between 95 and 105% for the different concentrations. The linearity of this assay was set between 25 and 800 microg/l (r(2)>0.999 of the regression line). The first results of pharmacokinetic analysis of midazolam indicated that half-life varied between 1.1 and 1.9 h. Pharmacokinetic analysis using a one-compartment model of levomepromazine revealed that the apparent volume of distribution was 4.1+/-2.4 l per kg lean body mass and the metabolic clearance was 309+/-225 l per hour per 70 kg. This assay proved to be robust and reproducible. It can reliably be used for further study of the pharmacokinetics of continuous infusion of levomepromazine.     

Preclinical pharmacokinetics and tissue distribution of a natural cardioprotective agent astragaloside IV in rats and dogs

Astragaloside IV, a natural product purified from the Chinese medical herb Astragalus membranaceus (Fisch) Bge, is now being developed as a cardioprotective agent for treating cardiovascular diseases. The purpose of the present study was to examine in vivo pharmacokinetics and tissue distribution in both rats and dogs by using an established high-performance liquid chromatography (HPLC) coupled with tandem mass spectrometry quantitative detection method. Astragaloside IV showed moderate to fast elimination; the elimination half-life of astragaloside IV was 98.1, 67.2 and 71.8 min in male rats, and 34.0, 66.9 and 131.6 min in female rats at doses of 0.75, 1.5 and 3.0 mg/kg, respectively. There was no significant difference in systemic clearance at three dose levels, suggesting that astragaloside IV may have linear pharmacokinetic characteristics in rats within the dose ranges tested. The highest concentration of astragaloside IV was detected in the lung and liver. However, limited distribution to the brain, indicates that astragaloside IV may have difficulty penetrating the blood brain barrier. In addition, only about 50% of the parent astragaloside IV was recovered in both urine and feces. These results indicate that there was about 83% astragaloside IV binding to plasma protein and that the binding to the plasma is linear at the concentration range of 250-1000 ng/ml. As in rats, astragaloside IV may have linear pharmacokinetic characteristics in dogs within the dose ranges tested. Astragaloside IV was slowly cleared via hepatic clearance with a systemic clearance (CL) of about 0.004 l/kg/min. Based on the favorable pharmacokinetic properties in both rats and dogs, astragaloside IV warrants further investigation for the prevention of cardiovascular diseases.     

Preparation, characterization, and in vivo evaluation of salmon calcitonin microspheres

Purpose. This study was done to prepare, characterize, and evaluate salmon calcitonin (sCT) microspheres (ms) in vivo using a low molecular weight, hydrophilic 50∶50 poly (D,L-lactide-co-glycolide) polymer (PLGA).Methods. sCT ms were prepared by a dispersion/solvent extraction/evaporation process and characterized for drug content, particle size, surface morphology, and structural integrity of encapsulated peptide. Peptide stability and binding to the polymer was studied in 0.1 M phosphate buffer (PB), pH 7.4, and 0.1 M acetate buffer (AB), pH 4.0. Serum sCT levels were monitored for 2 weeks after subcutaneous injection of sCT ms to rats.Results. sCT ms were essentially free of discernible surface pores with a particle size distribution in the range of 16 to 89 mm and mean particle size of 51 and 53 mm for 2 batches. Fourier Transform Matrix-assisted Laser Desorption mass spectrometry of the extracted peptide showed that the encapsulation process did not alter its chemical structure. The peptide was substantially more stable in AB than in PB. Peptide binding to the polymer was dependent on pH and was markedly higher in PB than in AB. In vivo study proved that elevated serum sCT levels could be sustained for at least 10 days after administration of sCT ms to rats at a dose of 1.0 mg/kg.Conclusions. It was demonstrated that sCT could be incorporated into polymeric ms prepared from a low molecular weight, hydrophilic PLGA using a dispersion technique without altering molecular structure. A 2-week formulation was prepared at a dose of 1.0 mg/kg.     

Quantitative determination of helicid in rat plasma by liquid chromatography-electrospray ionization mass spectrometry and its application to preliminary pharmacokinetic studies

A sensitive and selective liquid chromatography-electrospray ionization mass spectrometry (LC-ESI-MS) method was developed for the identification and quantification of helicid in rat plasma. The method was based on simple liquid-liquid extraction (LLE). A Kromasil C18 column (150mmx2.00mm, 3.5microm) was used as the analytical column, while a mixture of acetonitrile and 500microM ammonium chloride was used as the mobile phase. MS detection was performed using a single quadrupole mass spectrometer in a negative selected ion monitoring (SIM) mode. The deprotonated molecules [M+Cl](-) at m/z 319.00 and 363.05 were used to quantify helicid and bergeninum (internal standard, I.S.), respectively. The lower limit of quantification of helicid was 1ng/ml. The method was linear in the concentration range of 1-1000ng/ml. The intra-day and inter-day precisions (R.S.D.%) were within 10.0% for the analyte. Helicid proved to be stable during all sample storage, preparation and analytical periods. The method was successfully applied to a pharmacokinetic study in rats after intragastric administration of helicid with a dose of 50mg/kg. Only 50microl of rat plasma at each sampling time was needed for analysis. The proposed method enables unambiguous identification and quantification for the preliminary pharmacokinetic studies of helicid.     

Pharmacokinetics, Tissue Distribution, and Plasma Protein Binding Study of Platinum Originating from Dicycloplatin, a Novel Antitumor Supramolecule, in Rats and Dogs by ICP-MS

Dicycloplatin, as a new antitumor supramolecule, was considered to have higher solubility and higher stability compared with carboplatin. The aim of the present study was to evaluate the pharmacokinetic characteristics of platinum originating from dicycloplatin. A rapid, sensitive, and specific method with inductively coupled plasma mass spectrometry (ICP-MS) has been developed for the determination of platinum in bio-samples. The study was performed in male rats and dogs at a single dose of 10 and 5 mg kg(-1) separately by intravenous injection. Pharmacokinetic parameters were calculated by non-compartmental method, and the dose of platinum was used in the calculation of these parameters. Results showed that plasma concentrations of platinum began to decrease rapidly initially but decline slowly with a long terminal phase. The mean half-life was 27.39 and 100.98 and clearance was 0.77 and 0.08 L/h/kg for rats and dogs separately. Tissue distribution showed that platinum originating from dicycloplatin had a certain distribution in testis and prostate. Plasma protein binding proportion of platinum was increased with time. In conclusion, this research investigated the pharmacokinetic characteristics including plasma kinetics, tissue distribution, and plasma protein binding of platinum originating from dicycloplatin in rats and dogs in detail for the first time by ICP-MS.     

Determination of epimedin C in rat plasma by reversed-phase high-performance chromatography after oral administration of Herba Epimedii extract

A simple high-performance liquid chromatographic (HPLC) method has been developed for the determination of epimedin C in rat plasma and applied to a pharmacokinetic study in rats after administration of Herba Epimedii extract. After addition of carbamazepine as an internal standard plasma samples were extracted with ethyl acetate. HPLC analysis of the extracts was performed on a Hypersil ODS2 analytical column using acetonitrile -0.4% acetic acid (25:75, v/v) as the mobile phase. The UV detector was set at 260 nm. The standard curve was linear over the range 0.05-4.0 microg/mL. The lower limit of quantification was 0.05 microg/mL. The HPLC method developed could be easily applied to the determination and pharmacokinetic study of epimedin C in rat plasma after giving the animals Herba Epimedii extract.     

Stereospecific analysis of sakuranetin by high-performance liquid chromatography: pharmacokinetic and botanical applications

A stereospecific method for analysis of sakuranetin was developed. Separation was accomplished using a Chiralpak AD-RH column with UV (ultraviolet) detection at 288 nm. The stereospecific linear calibration curves ranged from 0.5 to 100 microg/mL. The mean extraction efficiency was >98%. Precision of the assay was <12% (relative standard deviation (R.S.D.)%), and within 10% at the limit of quantitation (0.5 microg/mL). Bias of the assay was lower than 10%, and within 5% at the limit of quantitation. The assay was applied successfully to pharmacokinetic quantification in rats, and the stereospecific quantification in oranges, grapefruit juice, and matico (Piper aduncum L.).     

Simple quantification of lansoprazole and rabeprazole concentrations in human serum by liquid chromatography/tandem mass spectrometry

A rapid, simple and highly sensitive method was developed for the quantitative determination of lansoprazole and rabeprazole concentrations in 20 microL of human serum using high-performance liquid chromatography/tandem mass spectrometry (LC/MS/MS). Analytes, along with an internal standard (lansoprazole deuterium derivatives), were separated using a mobile phase of acetonitrile/1mM ammonium formate (140/60, v/v) on a C18 analytical column and analyzed in the selected reaction-monitoring (SRM) mode. The lower limit of quantification was 0.25 ng/mL. A good linear response was observed for each analyte (from 0.25 ng to 2.5 microg/mL). This method was useful for therapeutic drug monitoring and pharmacokinetic studies.     

A new high performance liquid chromatographic method for quantification of atomoxetine in human plasma and its application for pharmacokinetic study

Atomoxetine is the first, non-stimulant alternative to other stimulant medications used for the treatment of Attention-Deficit/Hyperactivity Disorder (ADHD). Reported methods for the determination of atomoxetine include expensive liquid chromatography tandem mass spectrometry (LCMS) and high performance liquid chromatography (HPLC) with liquid scintillation counting (LSC) detection. Till date, no method has been reported in literature to determine atomoxetine using HPLC with UV detection. In this paper, we describe a new HPLC method for the determination of atomoxetine using liquid-liquid extraction with tertiary butyl methyl ether and UV detector. This method was found to be linear over the concentration range of 0.05-3.0 microg/ml. The limit of quantification was 0.05 microg/ml. Intra- and inter-day precision was <15% and accuracy was in the range of 95.67-108.80%. Stability studies showed that atomoxetine was stable in human plasma for short- and long-term period for sample preparation and analysis. This method was used for sample analysis in a pharmacokinetic study of atomoxetine (25mg) in five healthy adult female volunteers. The observed mean+/-S.D. pharmacokinetic parameters Cmax, Tmax and AUC(0-t) were 0.40+/-0.06 microg/ml, 3.40+/-0.42 h and 1.34+/-0.52 microg h/ml, respectively.     

Simultaneous determination of three residual barbiturates in pork using accelerated solvent extraction and gas chromatography-mass spectrometry

A new method was developed for the rapid extraction and unequivocal determination of barbital, amobarbital and phenobarbital residues in pork. The isolation of the analytes from pork samples was accomplished by utilizing an accelerated solvent extractor ASE 300. The procedure was automatically carried out in series for fat removing and extraction, respectively with n-hexane and acetonitrile pressurized constantly at 10.3 MPa for 30 min. After evaporation, the extracts were cleaned up on a C(18) solid phase extraction (SPE) cartridge and the barbiturates were eluted with hexane-ethyl acetate (7:3), evaporated on a rotary evaporator and derivatized with CH(3)I. The methylated barbiturates were separated on a HP-5MS capillary column and detected with a mass detector. Electron impact ion source (EI) operating in time program-selected ion monitoring mode (SIM) was used for identification and external standard method was used for quantification. Good linearity was obtained in the range from 0.5 microg/kg to 25 microg/kg. Average recoveries of the three barbiturates spiked in pork ranged from 84.0% to 103.0%, with relative standard deviations from 1.6% to 12%. The limit of detection (LOD) was 0.5 microg/kg for the three barbiturates (S/N>or=3). The quantification limit (LOQ) was 1 microg/kg for the three barbiturates (S/N>or=10).     

Histamine H1 receptors mediate the anorectic action of the pancreatic hormone amylin

We investigated the role of histamine H1 receptors in mediating the anorectic effect of intraperitoneally injected amylin (5 and 20 microg/kg), the amylin agonist salmon calcitonin (sCT; 10 microg/kg), leptin (1.3 mg/kg), and cholecystokinin (CCK; 20 microg/kg). The experiments were performed with mice lacking functional H1 receptors (H1Rko) and wild-type (WT) controls. The mice were also injected with the H3 antagonist thioperamide (20 mg/kg), which reduces feeding by enhancing the release of endogenous histamine through presynaptic H3 receptors. The feeding-suppressive effect of thioperamide was abolished in H1Rko mice. The anorectic effects of amylin and sCT were significantly reduced in 12-h food-deprived H1Rko mice compared with WT mice [1-h food intake: WT-NaCl 0.51 +/- 0.05 g vs. WT-amylin (5 microg/kg) 0.30 +/- 0.06 g (P < 0.01); H1Rko-NaCl 0.45 +/- 0.05 g vs. H1Rko-amylin 0.40 +/- 0.04 g; WT-NaCl 0.40 +/- 0.09 g vs. WT-sCT (10 microg/kg) 0.14 +/- 0.10 g (P < 0.05); H1Rko-NaCl 0.44 +/- 0.08 g vs. H1Rko-sCT 0.50 +/- 0.06 g]. The anorectic effect of leptin was absent in ad libitum-fed H1Rko mice, whereas CCK equally reduced feeding in WT and H1Rko animals. This suggests that the histaminergic system is involved in mediating the anorectic effects of peripheral amylin and sCT via histamine H1 receptors. The same applies to leptin but not to CCK. H1Rko mice showed significantly increased body weight gain compared with WT mice, supporting the role of endogenous histamine in the regulation of feeding and body weight.     

Ultra-performance liquid chromatography-tandem mass spectrometric method for the determination of Artemisinin in rat serum and its application in pharmacokinetics

A rapid and sensitive ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed and validated to quantify artemisinin in rat serum. The lower limit of quantification (LLOQ) was 4 ng/mL. The calibration curve was linear from 4 ng/mL to 10,000 ng/mL (R=0.998). The assay was based on the selected reaction monitoring (SRM) transitions at m/z 305.4-151.10 for artemisinin and m/z 335.2-163.10 for arteether (internal standard). The artemisinin and internal standard can be separated from endogenous interferences in rat serum. Inter- and intra-day assay variation was less than 15%. The extraction recoveries ranged from 80.0 to 107.3% at the three concentrations (5000, 2000, and 200 ng/mL). This method was successfully applied to pharmacokinetic studies of artemisinin after intravenous and oral administration to rats.