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Jingkai Gu

Publications and source records attributed to Jingkai Gu.

16 recordsLinked to original sources

Determination of miglitol in human plasma by liquid chromatography/tandem mass spectrometry.

A rapid and sensitive method for the determination of miglitol in human plasma using voglibose as internal standard has been developed and validated. Samples of plasma were deproteinated with acetonitrile and washed with dichloromethane before being analyzed by reversed-phase high-performance liquid chromatography (HPLC). Separation was carried out on a short Nucleosil C(18) column (5 microm, 50 x 4.6 mm i.d.) using 10 mmol/L ammonium acetate at 1.0 mL/min as mobile phase. The detector was an Applied Biosystems Sciex API 4000 mass spectrometer using atmospheric pressure chemical ionization (APCI) for ion production. The instrument was operated at unit resolution in the multiple reaction monitoring mode. The assay was linear over the range 5.00-2000 ng/mL with a limit of detection of 1.00 ng/mL. Intra- and inter-day precision were <2.82% and <2.92%, respectively, with accuracy of 93.3-106%. The assay was successfully applied to a clinical pharmacokinetic study of miglitol given as a single oral dose (50 mg) to healthy volunteers.

1-Deoxynojirimycin↗

Determination of clarithromycin in human plasma by liquid chromatography-electrospray ionization tandem mass spectrometry.

A rapid and sensitive method has been developed for the determination of clarithromycin in human plasma with liquid chromatography-tandem mass spectrometry. Clarithromycin and the internal standard, telmisartan were precipitated from the matrix (50 microl) with 200 microl acetonitrile and separated by HPLC using formic acid:10 mM ammonium acetate:methanol (1:99:400, v/v/v) as the mobile phase. The assay based on detection by electrospray positive ionization mass spectrometry in the multiple-reaction monitoring mode was finished within 2.4 min. Linearity was over the concentration range 10-5000 ng/ml with a limit of detection of 0.50 ng/ml. Intra- and inter-day precision measured as relative standard deviation were <3.73% and <9.93%, respectively. The method was applied in a bioequivalence study of two tablet formulations of clarithromycin.

Anti-Bacterial Agents↗

Liquid chromatographic/tandem mass spectrometric method for the quantitation of tranilast in human plasma.

An analytical method for the determination of tranilast in human plasma using tramadol as the internal standard has been developed based on liquid chromatography/tandem mass spectrometry. Sample preparation involved protein precipitation with methanol. Separation by reversed-phase high-performance liquid chromatography using methanol/10 mM ammonium acetate (70: 30, v/v) as mobile phase was complete in a run time of 2.4 min. Detection on a Q TRAP system used multiple reaction monitoring. The method was linear in the range 0.06-20 microg/mL with intra- and inter-day precisions (as relative standard deviation) of 2.2-2.6% and 2.3-2.9%, respectively. Accuracy (as relative error) was <-2.5%. The method was applied in a pharmacokinetic study in healthy volunteers treated with a single 80 mg oral dose of tranilast.

Administration, Oral↗

Pharmacokinetics of huperzine A in dogs following single intravenous and oral administrations.

The pharmacokinetics of huperzine A in dogs after single intravenous and oral administrations was investigated. Concentrations of huperzine A were determined by a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. Pharmacokinetic parameters were calculated by non-compartmental methods. After single intravenous administration, the Cmax, T1/2, AUC0-t, AUC0-infinity, CL, Vd and Vss were 5.55 +/- 1.61 microg/L, 5.02 +/- 0.31 h, 16.04 +/- 5.24, 16.49 +/- 5.29 microgh/L, 0.66 +/- 0.19 L/h/kg, 4.76 +/- 1.46, and 3.93 +/- 1.54 L/kg, respectively. After single oral administration, the Cmax, Tmax, T1/2, AUC0-t, AUC0-infinity and oral bioavailability were 2.60 +/- 0.60 microg/L, 1.25 +/- 0.50 h, 5.71 +/- 2.25 h, 12.90 +/- 3.19, 13.78 +/- 3.24 microgh/L, and 94.4 +/- 36.5%, respectively. In conclusion, huperzine A had a rapid and nearly complete oral absorption and was extensively distributed into tissues after drug administration in dogs.

Administration, Oral↗

Liquid chromatographic-tandem mass spectrometric method for the quantitation of sildenafil in human plasma.

A method to determine sildenafil in human plasma involving liquid chromatography-tandem mass spectrometry (LC-MS/MS) has been developed. Sildenafil and the internal standard (I.S.), diazepam, are extracted from human plasma with ether-dichloromethane (3:2, v/v) at basic pH and analyzed by reversed-phase high-performance liquid chromatography (HPLC) using methanol-10mM ammonium acetate pH 7.0 (85:15, v/v) as the mobile phase. Detection by electrospray positive ionization mass spectrometry in the multiple-reaction monitoring mode was linear over the concentration range 0.125-40.0 ng/ml. Intra- and inter-day precision of the assay at four concentrations within this range were 2.5-8.0%. The method was used to evaluate plasma concentration-time profiles in healthy volunteers given an oral dose of 20mg sildenafil as a combination tablet also containing apomorphine.

Chromatography, High Pressure Liquid↗

Determination of telmisartan in human plasma by liquid chromatography-tandem mass spectrometry.

A rapid, selective and sensitive method for the determination of the angiotensin II receptor antagonist, telmisartan, in human plasma has been developed. Telmisartan and the internal standard, diphenhydramine, were extracted from plasma using diethyl ether-dichloromethane (60:40, v/v), and separated on a Zorbax extend C(18) column using methanol-10mM ammonium acetate (85:15, v/v) adjusted to pH 4.5 after mixing with formic acid as mobile phase. Detection was carried out by multiple reaction monitoring on a Q-trap LC-MS/MS system with an ESI interface. The assay was linear over the range 0.5-600.0 ng/ml with a limit of quantitation of 0.5 ng/ml and a limit of detection of 0.05 ng/ml. Intra- and inter-day precision were <6.7% and <8.1%, respectively, and the accuracy was in the range 88.9-111.0%. The assay was applied to a pharmacokinetic study of telmisartan given as a single oral dose (80 mg) to healthy volunteers.

Benzimidazoles↗

Determination of omeprazole in human plasma by liquid chromatography-electrospray quadrupole linear ion trap mass spectrometry.

An analytical method for the determination of omeprazole in human plasma has been developed based on liquid chromatography mass spectrometry. The analyte and internal standard sildenafil are extracted from plasma by liquid-liquid extraction using diethyl ether:dichloromethane (60:40, v/v) and separated by reversed phase high-performance liquid chromatography (HPLC) using acetonitrile:methanol:10 mM ammonium acetate (37.5:37.5:25, v/v/v) as mobile phase. Detection is carried out by multiple reaction monitoring on a Q TRAP LC/MS/MS system (Q TRAP). The method has a chromatographic run time of 3.5 min and is linear within the range 0.50-800 ng/mL. Intra- and inter-day precision expressed as relative standard deviation ranged from 0.4 to 8.5% and from 1.2 to 6.8%, respectively. Assay expressed as relative error was <5.7%. The method has been applied in a bioequivalence study of two capsule formulations of omeprazole.

Calibration↗

Rapid and sensitive liquid chromatography-tandem mass spectrometry method for the quantitation of levodropropizine in human plasma.

A rapid and sensitive LC-MS-MS method for quantifying levodropropizine in human plasma after oral administration of a single-dose (60 mg/day) was developed and validated. The sample preparation used liquid-liquid extraction with a mixture of dichloromethane-diethyl ether (2:3, v/v) in a basic environment. The retention time of levodropropizne and zolmitriptan (used as internal standard) was 1.6 and 1.4 min, respectively. The assay was linear over the range 0.25-500 ng/mL with a LOQ of 0.25 ng/mL. The intra- and inter-day precision were < 8.1% and < 11.5%, respectively, and the accuracy was in the range 87.6-112%. The levodropropizine concentration profile in human plasma was determined.

Antitussive Agents↗

Determination of dioscin in rat plasma by liquid chromatography-tandem mass spectrometry.

A sensitive and specific high-performance liquid chromatography-tandem mass spectrometric (LC-MS/MS) assay for dioscin in rat plasma was developed. Ginsenoside Rh2 was employed as an internal standard. Dioscin is a naturally occurring saponin present in many traditional Chinese medicinal plants. Dioscin was determined after the acetonitrile-mediated plasma protein precipitation. The mobile phase consisted of acetonitrile:10 mmol/l aqueous ammonium acetate (95:5, v:v), which was pumped at 0.8 ml/min. The analytical column (100 mm x 4.6 mm i.d.) was packed with Hypersil ODS material (5 microm). The standard curve was linear from 1 to 100 ng/ml. The assay was specific, accurate (percentage deviations from nominal concentrations were <10%), precise and reproducible (within- and between-day coefficients of variation <10%). Dioscin in rat plasma was stable over three freeze-thaw cycles and at ambient temperatures for 24 h. The utility of the assay was demonstrated by determining dioscin plasma concentrations in five rats for 120 h following a single oral gavage dose of 90 mg/kg.

Animals↗

Characterization of the pharmacokinetics of dioscin in rat.

Dioscin (diosgenyl 2,4-di-O-alpha-l-rhamnopyranosyl-beta-d-glucopyranoside) is an important constituent of some traditional Chinese medicines with several bioactivities. We have investigated the pharmacokinetics of dioscin in rat after intravenous and oral administrations. Compartmental methods were used to perform pharmacokinetic data analysis. The dose-dependent pharmacokinetics of dioscin was characterized after intravenous administrations (0.064, 0.16, 0.4 and 1.0mg/kg) to rats. There was significant decrease in clearance with increasing dose (4.67+/-0.09 ml/min/kg (0.064 mg/kg) versus 3.49+/-0.23 ml/min/kg (1.0 mg/kg), P<0.05), and the plot of reciprocal clearance values versus the doses was linear (r=0.909, P<0.05). After an I.V. dose of 1mg/kg, simultaneous oral gavage of activated charcoal did not change the pharmacokinetic parameters indicating enterohepatic recycling of dioscin is not important in rat. The absolute oral bioavailability was very low (0.2%). In tissue distribution and bile excretion studies after I.V. and oral administrations, dioscin was shown to undergo a prolonged absorption from the intestinal tract and slow elimination from organs, and only a small amount of drug was recovered in bile. The cumulative amounts of dioscin in feces and urine indicated that the parent drug is mainly excreted in the feces.

Administration, Oral↗

Rapid and sensitive liquid chromatography-tandem mass spectrometric method for the quantitation of metformin in human plasma.

A rapid and sensitive liquid chromatography-tandem mass spectrometric (LC-MS-MS) method for the determination of metformin in human plasma using phenformin as internal standard has been developed and validated. Sample preparation of plasma involved acidification with acetic acid, deproteination with acetonitrile and washing with dichloromethane. Samples were then analyzed by HPLC on a short Nucleosil C18 column (5 microm, 50 mm x 4.6 mm i.d.) using a mobile phase consisting of acetonitrile:methanol:10mM ammonium acetate pH 7.0 (20:20:60, v/v/v) delivered at 0.65 ml/min. Detection was performed using an Applied Biosystems Sciex API 4000 mass spectrometer set at unit resolution in the multiple reaction monitoring (MRM) mode. Atmospheric pressure chemical ionization (APCI) was used for ion production. The assay was linear over the range 1-2000 ng/ml with intra- and inter-day precision of <8.6% and accuracy in the range 91-110%. The limit of detection was 250 pg/ml in plasma. The method was successfully applied to a clinical pharmacokinetic study of an extended-release tablet of metformin hydrochloride (500 mg) administered as a single oral dose.

Chromatography, High Pressure Liquid↗

Liquid chromatographic-tandem mass spectrometric method for the quantitation of huperzine A in dog plasma.

A rapid and sensitive LC-MS-MS method for the determination of huperzine A in dog plasma using huperzine B as internal standard has been developed and validated. The analyte and internal standard were extracted from plasma using n-hexane-dichloromethane-2-propanol (300:150:15, v/v/v), chromatographed on a C(18) column (5 microm, 50 mm x 4.6 mm i.d.) with a mobile phase consisting of acetonitrile-methanol-10mM ammonium acetate (35:40:25, v/v/v), and detected using a tandem mass spectrometer with a TurboIonSpray ionization interface. The run time was only 2 min. The assay was linear over the concentration range 0.05-20 ng/ml and intra- and inter-day precision over this range were <5.3% with good accuracy. The limit of detection in plasma was 0.01 ng/ml. The method was successfully applied to define plasma concentration-time curves of huperzine A in dogs after the last dose of an intramuscular injection (10 microg/kg per day for 15 days) of a sustained-release formulation of huperzine A.

Alkaloids↗

Sensitive liquid chromatographic assay for the simultaneous determination of 5-fluorouracil and its prodrug, tegafur, in beagle dog plasma.

A high-performance liquid chromatographic (HPLC) method has been developed for the simultaneous determination of 5-fluorouracil (5-FU) and its prodrug, tegafur (TF), in dog plasma. 5-FU, the internal standard, 5-bromouracil, and TF were separated on a C18 Spherisorb ODS2 column using isocratic elution with retention times of 4.4, 8.0 and 21.2 min, respectively. Detection by UV absorption at 260 nm gave a limit of quantitation of 4 microg/l for 5-FU in plasma. Calibration curves for 5-FU and TF were linear over the ranges of 4-160 microg/l and 0.48-19.2 mg/l, respectively. Intra- and inter-day precision over these concentration ranges were <10.9 and <13.6% for 5-FU and TF, respectively, with good accuracy for both compounds. The method was successfully applied to define plasma concentration-time curves of TF and 5-FU in dogs administered a single oral dose containing TF (100 mg) and uracil (224 mg).

Animals↗

Determination of ketotifen and its conjugated metabolite in human plasma by liquid chromatography/tandem mass spectrometry: application to a pharmacokinetic study.

A sensitive and specific liquid chromatography/tandem mass spectrometry (LC/MS/MS) method was developed for the investigation of the pharmacokinetics of ketotifen and its major metabolite, ketotifen N-glucuronide, in human plasma. The plasma samples were treated by liquid-liquid extraction and analyzed using LC/MS/MS with an electrospray ionization interface. Diphenhydramine was used as the internal standard. The method had a lower limit of quantitation of 10 pg/mL for ketotifen, which offered increased sensitivity, selectivity and speed of analysis, compared with existing methods. The intra- and inter-day precision were measured to be below 8.2% and accuracy between -2.4% and 3.4% for all QC samples. Incubation of the plasma samples with beta-glucuronidase allowed the quantitation of ketotifen N-glucuronide. This quantitation method was successfully applied to a pharmacokinetic study of ketotifen and its major metabolite after oral administration of 2 mg ketotifen fumarate to 16 healthy volunteers.

Adult↗

Isolation and identification of the glucuronide of 4-(3H-1,2-dihydro-1-pyrrolizinone-2-methylamino)benzoic acid from rabbit urine.

The metabolic profile of 3H-1,2-dihydro-2-(4-methylphenylamino)methyl-1-pyrrolizinone (SFZ-47), a putative non-steroidal anti-inflammatory pro-drug, has been studied in rabbit urine. Semi-preparative reversed-phase HPLC of 24 h urine from two rabbits given single oral doses of SFZ-47 (200 mg) allowed the separation of SFZ-47 together with the oxidative metabolite 4-(3H-1,2-dihydro-1-pyrrolizinone-2-methylamino)benzoic acid (SFZ-47-COOH) and its glucuronide conjugate. The glucuronide was characterized by ESI-MS(n) and (1)H NMR and shown to be the 1-O-acyl beta-D-glucuronide conjugate of SFZ-47-COOH. The method gave excellent resolution of the glucuronide from endogenous constituents in urine and may be suitable for the preparation of glucuronide metabolites of other drugs.

Animals↗