流体动力色谱法和障碍色谱法及其应用

介绍了流体动力色谱(HDC)和障碍色谱(SC)及其在生物、化工分离中的研究进展,着重于它们的分离原理、理论发展及二者之间的联系与转化,引用52篇文献。

Pharmacokinetics of Scutellarin in Dogs

Aim To establish an RP-HPLC method for the determination of scutellarin in plasma and study its pharmacokinetics in dogs. Methods Scutellarin was given to dogs by intravenous injection and determined by RP-HPLC, the mean plasma concentration-time curve was plotted and pharmacokinetic parameters were calculated by program 3p87. Resu;ts The concentration-time curve of scutellarin could be fitted to three-compartment model with T1/2 pi, T1/2 α and T1/2 β being 1.05 ± 0.80 min, 6.99 + 2.76 min and 51.61 + 28.78 min, respectively, Vc being 880.1 + 508.3 mL, CL being 189.6 + 53.8 mL@ min- 1, and AUC0-90 and AUC0-∞ being 574.43 + 133.95 μg@ min@ mL - 1 and 599.34 ± 132.00μg@ min@mL- 1, respectively. Conclusion The fact that the concentrations of scutellarin in plasma declined rapidly after the medication suggested that the T1/2 of scutellarin should be taken into account in drug administration and preparation development.

Pharmacokinetics of Ferulic Acid in Rabbits with BloodStasis

To test and study the Syndrome and Treatment Pharmacokinetics (S & TRK),we studied the pharmacokinetics of ferulic acid in healthy and blood stasis (microcirculation dysfunction)rabbits by RP-HPLC. After a single intravenous injection offenilic acid(5mg/kg)to healthy and blood stasis rabbits, compartment model of ferulic acid serum concentration was fitted and then pharmacokinetic parameters were calculated with a MCPKP program on a COMPAQ 386 compute Important parameters are as follows: In healthy rabbits V_B=0.9525±0.0211 L/kg,V_1=0.2462±0.0381 L/kg, CL_B=1.8133±0.9512 L/h·kg, T_(1/2β)=0.3639±0913, AUC=2.7566±0.8232 μg·h/ml; In blood stasis rabbits V_B=0.7882±0.0321 L/kg,V_1=0.1966±0.0537 L/kg,CL_B=0.8820±0.5481 L/h·kg,T_(1/2β)=0.6193±0.1216 h, AUC=5.6690±2.3541μg·h/ml.Through this experiment we found the sig-nificant differences in the FA's pharmacokinetic parameters between healthy and blood stasis rabbits.The results obtained correspond with S & TPK.

Pharmacokinetics of Oxiracetam in Healthy Volunteers

Aim To study the pharmacokinetics of oxiracetam after single and multipleintravenous administrations in healthy volunteers. Method A HPLC method was used to determine theserum concentration of oxiracetam after intravenous single dose and daily dose of 2 000 mg for 7 din ten Chinese healthy volunteers. Pharmacokinetic analysis was carried out using Drug And Statisticsoftware. Results The AUC_(0-12), AUC_(0-∞), K_e, t_(1/2), MRT after a single dose of 2 000 mgoxiracetam were 256.26 ± 16.84 μg·mL^(-1)·h, 276.74 ±18.11 μg·mL^(-1)·h, 0.18 ±0.03 h^(-1),3.84±0.64 h, and 4.39 10.39 h, and after multiple doses of oxiracetam were 259.36 ±25.43μg·mL^(-1)·h, 285.59 ±27.38 μg·mL^(-1)·h, 0.17 ±0.04 h^(-1), 4.14 ± 0.82 h, and 4.87 ±0.69 h, respectively. Conclusion The pharmacokinetic parameters of oxiracetam do not differremarkably after single and multiple intravenous administration and there is accumulation in serumafter 2 000 mg multiple intravenous administration once a day fof 7 d.

Determination of Lansoprazole by Direct Injection of Plasma and High Performance Liquid Chromatography with Column Switching

High performance liquid chromatography with column switching has been developed for the determination of lansoprazole in plasma. The plasma samples were injected onto a pretreatment column packed with LiChromprep RP2 (25～40 mm) after simple dilution with distilled water. Distilled water was used to wash out protein and other polar components in plasma. After switching, the concentrated lansoprazole was eluted in the backflush mode onto a Shimpack CLC ODS column with methanol 0 2 mol·L 1 ammonium acetate (65:35) as mobile phase. Purge solutions were used for clean up and for regenerating the pretreatment column. The method showed good precision and recovery. The detection limit was 0 005 mg·L -1 plasma. The RSD’s (intra and interday) were less than 2 5% and 5 3% respectively. The method has been successfully used to determine pharmacokinetics of lansoprazole in Chinese volunteers.

Pharmacokinetics of Active Metabolite of Prulifloxacin in Healthy Chinese

Aim To investigate the pharmacokinetics of NM394 （an active metabolite of prulifloxacin） and evaluate the dose relationship and accumulation characteristics after single and multiple doses of prulifloxacin. Methods Twelve healthy volunteers were given 132.1 mg, 264.2 mg, and 396.3 mg of prulifloxacin tablets in a randomized 3 × 3 crossover design test for single doses trial. With one-week washout period, 264.2 mg of prulifloxacin tablets were given for multiple doses trial. NM394 in plasma was determined by a sensitive HPLC method and its pharmacokinetic parameters were analyzed and evaluated by Drug and Statistics saftware （version 1.0）. Results The Cmax, Tmax, t 1/2, AUC0-24, and AUC0-∞ of NM394 after single doses of 132.1 mg, 264.2 mg, and 396.3 mg of prulifloxacin tablets were 0.64 ± 0.25 μg· mL^-1, 1.06 ± 0.35 μg· mL^-1, and 1.45 ± 0.44 μg· mL^-1 , respectively; Tmax 0.94±0.22 h, 1.02±0.17 h, and 0.98±0.23 h, respectively; t 1/2 8.37±0.70 h, 7.70±0.82 h, and 7.78 ± 0.77 h, respectively; AUC0-24 2.93 ± 0.78 μg· mL^-1· h, 4.39 ± 1.05 μg· mL^-1· h, and 5.55± 1.32 μg·mL^-1 ·h, respectively; AUC0-∞ 3.32±0.84 μg·mL^-1 ·h, 4.82± 1.06 μg·mL^-1 ·h, and 6.10 ± 1.38 μg·mL^-1· h, respectively. And the Cmax, Tmax, t,1/2, AUC0- 24, and AUC0-∞ after multiple doses of 264.4 mg prulifloxacin tablets were 1.20 ± 0.33 μg· mL^- 1, 0.67 ± 0.12 h, 7.38 ± 1.03 h, 5.58 ± 1.25 μg· mL^-1·h, and 6.09 ± 1.24 μg· mL^-1· h, respectively. Conclusion The Cmax and AUC of NM394 are in high correlation with given prulifloxacin doses. There are no differences in pharnacokinetic characteristics of NM394 between single and multiple doses. No accumulation in plasma is observed after multiple doses of 264.2 mg per day for 7 d.

Determination of Naftopidil in Dog Plasma by High Performance Liquid Chromatography and Study on Its Pharmacokinetics

建立HPLC方法测定犬血浆中的萘哌地尔浓度，研究萘哌地尔胶囊在犬体内的药物动力学。单剂量给予5只健康犬萘哌地尔胶囊200mg,血浆样品碱化后，经乙醚提取以乙腈：磷酸盐缓冲液（0．05mol·L^-1的磷酸二氢钾溶液，以0．1mol·L^-1的NaOH调节pH至6．5）＝60：40（v/v)为流动相，由ODS C18分析柱分离测定，紫外230nm为检测波长，维拉帕米为内标。线性范围为10ng·L^-1;方法回收率为：100．23±3．00％；检测限：8ng·mL^-1;日间RSD≤5.56%,日内RSD≤3．30％。本法简便，回收率和灵敏度高，可用于萘哌地尔制剂的药动学研究。单剂量给予犬萘哌地尔胶囊200mg后血药浓度随时间变化规律符合一级吸收一室模型，T1／2Ke为3．19±1．27h,Tmax为1.15±0.59h,Cmax为697.48±94.22ng·mL^-1.

Determination of Diphenytriazol (DL111-IT) in Rabbit Plasma by High-Performance Liquid Chromatography with Fluorescence Detection

Aim To develop an HPLC method with fluorescence detection for the assay ofDL111-IT in rabbit plasma. Methods DL111-IT and internal standard glybenzcyclamide in rabbit plasmawere extracted with chloroform. The determination was performed on a Diamonsil ODS-C_(18) column(150 mm x 4.6 mm, 5 μm) with a mobile phase of acetonitrile and 0.025 mol·L^(-1) diammoniumhydrogen phosphate buffer (pH 5.0, adjusted by phosphoric acid) (60:40, V/V) at a flow-rate of 1.0mL·min^(-1) . Fluorescence detector was operated at excitation wavelength of 250 nm and emissionwavelength of 332 nm. Results The calibration curve in plasma was linear from 1.00 - 20.00ng·mL^(-1) ( r = 0.999 6, n = 5). The method afforded average extracting recoveries of 85.3% ±1.3%, 84.9% ± 2.7% and 85.8% ± 1.8%, and the average method recoveries were 99.5% ±0.4%, 102.1%± 1.8% and 101.3% ± 2.4% for the high (20.00 ng·mL^(-1)) , middle (10.00 ng·mL^(-1)) and low (1.00 ng·mL^(-1)) check samples, respectively. The intra-day (n = 5) and inter-day (n = 5) precisions(RSD) were less than 3.0% and 7.0%, respectively. The limit of detection and quantitation for themethod were 0.3 ng·mL^(-1) (S/N = 3) and 1 ng·mL^(-1) (S/N = 10, RSD<7.0%) plasma sample,respectively. Conclusion The developed method was accurate, sensitive, simple and could be used forpharmacokinetic study of DL111- IT.

Reaction Kinetics of Trans-Sobrerol and 8-p-Menthen-1,2-diol with Hydroxyl Radical in Aqueous Solution： A Combined Experimental and Theoretical Study

Trans-sobrerol （Sob） and 8-p-menthen-1,2-diol （Limo-diol） are the primary products in the atmospheric oxidation of α-pinene and limonene, respectively. Because of their low volatility, they associate more likely to the liquid particles in the atmosphere, where they are subject to the aqueous phase oxidation by the atmospheric oxidants. In this work, through experimental and theoretical study, we first provide the rate constants of Sob and Limo-diol reacting with hydroxyl radical （.OH） in aqueous solution at room temperature of 3044-3 K and 1 atm pressure, which are （3.05±0.5）×10 9 and （4.57±0.2）×10 9 L/（mol.s）, respectively. Quantum chemistry calculations have also been employed to demonstrate the solvent effect on the rate constants in aqueous phase and the calculated results agree well with the measurements. Some reaction products have been identified based on liquid chromatography combined with mass spectroscopy and theoretical calculations.

Pharmacokinetics and Bioavailability of 2-Amino-6-Cyclopropylamino-9-(2,3 -Dideoxy-β-D-glyceropent-2-enofuranosyl) Purine (Cyclo-D4G) in Rats

AimTo characterize the pharmacokinetics of 2 -amino-6-cyclopropylamino-9-(2,3-dideoxy-β-D-glyceropent-2-enofuran osyl) purine (Cyclo-D4G) following intravenous administration and oral administ ration to rats. MethodsThe concentrations of Cyclo-D4G in rat (Sprague-Dawley male rats) plasma and urine were analyzed by high performance liquid chromatography (HPLC). ResultsFollowing intravenous adm inistration to rats, concentrations of Cyclo-D4G in plasma declined with a term inal phase half-life of 0 78±0 14 h (±s). Total clearance was 0 90±0 21 L·h -1 ·kg -1 . Renal excretion of unchanged Cyclo-D4G accounted for approximately 20% of total clearance. Steady state volume of distr ibution was 0 91±0 07 L·kg -1 . After oral administration to rats, conce ntrations of Cyclo-D4G in plasma declined with a terminal phase half-life of 0 83±0 13 h (±s). Total clearance was 3 81±2 03 L·h -1 ·kg -1 . Renal excretion of unchanged Cyclo-D4G accounted for approximat ely 9% of total clearance. Oral bioavailability of Cyclo-D4G in rat was 26 9%. ConclusionThe favorable pharmacokinetic profiles and lower to xicity provide support for further development of Cyclo-D4G clinical trials.

Kinetics of water–isocyanate reaction in N,N-dimethylformamide

The uncatalyzed reaction of p-tolyl isocyanate(p-TI)with water in N,N-dimethylformamide(DMF)was investigated by high performance liquid chromatography(HPLC).The reactions were carried out at different temperatures from 293 K to 323 K,using various molar ratios of water to p-TI.DMF,as a special amide,was proved to be an efficient catalyst for water–isocyanate reaction.Under the reaction conditions in this study,substituted urea was the only final product observed.An appreciable amount of intermediate p-toluidine was detected.Concentrations of the isocyanate group as well as the amine and urea were determined as a function of time.New kinetic equations were deduced for each of the substance on the basis of a multistep mechanism,instead of a simple second order reaction as usual.Kinetic constants were calculated using the software MATLAB.Furthermore,the effects of temperature and concentrations of reactants on the reaction rate and amine content were discussed.The activation energy of each step was also determined.

Microanalysis and preliminary pharmacokinetic studies of a sulfated polysaccharide from Laminariajaponica

A rapid, sensitive and reproducible high performance liquid chromatography （HPLC） method with post-column fluorescence derivatization has been developed to determine the amount of low-molecular- weight sulfated polysaccharide （GFS） in vivo. The metabolism of GFS has been shown to fit a two component model following its administration by intravenous injection, and its pharmacokinetic parameters were determined to be as follows： half-time of distribution phase （t1/2α）=11.2±2.93 min, half-time of elimination phase （tl/2α）=98.20±25.78 min, maximum concentration （Cmax）=110.53 gg/mL and peak time （Tmax）=5 min. The pharmacokinetic behavior of GFS was also investigated following intragastric administration. However, the concentration of GFS found in serum was too low for detection, and GFS could only be detected for up to 2 h after intragastric administration （200 mg/kg body weight）. Thus, the bioavailability of GFS was low following intragastric administration because of the metabolism of GFS. In conclusion, HPLC with post-column derivatization could be used for quantitative microanalysis and pharmacokinetic studies to determine the presence of polysaccharides in the serum following intravenous injection.

Biodegradation of Acid Anthraquinone Dye in a Facultative-aerobic Process:Kinetics and Products

The transformation of an anthraquinone dye blue 324 in a facultative-aerobic(F-A) system was investigated.Kinetic parameter study showed that higher Vmax coupled with more recalcitrant chemical oxygen demand(COD) were found in the facultative biofilm reactor(FBR) than in the aerobic reactor(AR).Results of the product analyses indicated that most of dye molecular could be facultatively broken down into simple intermediates,which would be further degraded under subsequent aerobic condition.The main metabolites in each reactor were detected by infrared(FT-IR) and high performance liquid chromatography and mass spectrometry(HPLC-MS).Comparison of the toxicities among the dye and its metabolites was conducted,surprisingly,the colorless intermediates from FBR possessed less inhibitory than original dye and the median effective luminescence concentration(EC50) in 15 min for aerobic effluent could not be detected,showing that hardly toxic products existed in the aerobic process effluent.

A method for the quantitative determination of glycyrrhetic acid in plasma by LC-MS/MS and its application in a pharmacokinetic study of ammonium glycyrrhetate

A simple and rapid liquid chromatography-tandem mass spectrometry（LC-MS/MS）method was developed and validated for the quantitative determination of glycyrrhetic acid（GA）,metabolite of glycyrrhizin and glycyrrhetate,in human plasma.GA and internal standard（IS,thiamphenicol）were separated on a C_（18）column by elution with acetonitrile-ammonium acetate solution（5 mmol/L）（70：30,v/v）after a simple liquid-liquid extraction with ethyl acetate.The flow rate was 0.8 mL/min. They were detected by tandem mass spectrometry in the negative ion multiple reaction monitoring（MRM）mode with ion transitions of m/z 469.3→355.3 for GA and m/z 354.1→185.0 for IS.The calibration curve was linear over GA concentration range of 0.5-500 ng/mL（r^20.99）,with intra-and inter-day precisions（RSD）of less than 7.1%,and mean extraction recovery of 74.3%. The method was used for the pharmacokinetic study of ammonium glycyrrhetate after its oral administration of a single dose of 75 mg ammonium glycyrrhetate tablet in humans.The main pharmacokinetic parameters of GA were as follows：AUC_（0-t） （3457.26±1999.01）ng·h/mL;AUC_（0-∞）（3708.85±2428.36）ng·h/mL;MRT_（0-t）（19.69±4.03）h;MRT_（0-∞）（22.83±8.45）h;t_（1/2）Z （11.71±7.77）h;T_（max）（13.40±4.84）h;CLz/F（29.17±19.82）L/h;Vz/F（487.38±518.07）L;C_（max）（215.85±99.88）ng/mL.

A high performance liquid chromatography method for the quantitative determination of ribavirin in human plasma and its application in a pharmacokinetics study

The clinical pharmacokinetics of ribavirin after a single oral dose of 600 mg ribavirin tablets in healthy Chinese volunteers was studied. A rapid and simple high performance liquid chromatography （HPLC） method was developed to determine the ribavirin concentration in human plasma. C18 column was used for separation with a column temperature of 25℃, the mobile phase was ultrapure water adjusted to pH 3 with acetic acid at the flow rate of 1 mL/min, and the detection wavelength was set at 207 rim. The linear range of the standard curves was 50.4-2016.0 ng/mL and the lower limit of quantification （LLOQ） was 50.4 ng/mL. The relative recoveries of ribavirin were more than 90% in plasma. The RSD of the intra-day precision was less than 10% and that of inter-day was less than 15%. The pharmacokinetic parameters of ribavirin were calculated by WinNonlin. Results indicated that the two-compartment model was a better model for describing the pharmacokinetics profile of ribavirin than one-compartment model. The AUC0-t was 10807.8 h.ng/mL, the CL/F was 64879.5 mL, and the Cmax was 525.1 ng/mL. These results provided the experimental data for the development of ribavirin dosage form.

Pharmacokinetics of diclazuril after oral administration of clinical doses to rabbits

The purpose of this study was to evaluate the pharmacokinetic parameters and bioavailability of the solid dispersion formulation of diclazuril after oral administration in rabbits in comparison with its known premix form with feed additive.Plasma concentrations were determined by high-performance liquid chromatography（HPLC）.The areas under the plasma concentration curves（AUC0-∞） of diclazuril in solid dispersion and premix were 247.8±18.1μg/h/mL and 145.4±12.6μg/h/mL,respectively. The Cmax of diclazuril in solid dispersion and premix were 33.72±4.75 μg/mL and 10.42±3.4μg/mL, respectively, The t1/2 were 9.53±1.37 and 9.23±1.20 min, respectively. The oral bioavailability of drug solid dispersion was 1.7-fold higher than that of premix. From these data we concluded that diclazuril solid dispersion may be used as a potential anticoccidial preparation.

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.

HPLC-UV method with solid-phase extraction for the quantitative determination of biapenem in human plasma and its application in pharmacokinetic study

Biapenem, a new parenteral carbapenem, has been widely used for treating bacterial infections. A simple, effective and accurate method based on solid-phase extraction （SPE） and HPLC was developed for the quantitative determination of biapenem in human plasma. Stability and feasibility of the method was validated through a series of experiments. Using Vitamin B6 as an internal standard, analyte was separated on a Capcell Pak C18 column after SPE on Oasis hydrophilic-lipophilic balance （HLB） cartridge. The mobile phase was comprised of 0.05 mol/L NaH2PO4 （pH 5.7） and methanol （98：2, v/v） at a flow rate of 1.0 mL/min. Ultraviolet absorbance was measured at 300 nm. The calibration curve was linear in the concentration range of 0.04-50.00 μg/mL, and the lower limit of quantification was as low as 0.04 μg/mL. Recovery rates of biapenem at 0.10, 5.00, and 25.00 μg/mL were about 70%. The validated method has been successfully applied for quantifying biapenem in human samples and a pharmacokinetic study of 12 healthy volunteers who received three different doses （150, 300 and 600 mg） of biapenem by intravenous infusion. Our method has featured good accuracy and precision, and the processed sample was stable. Therefore, it can be propagated for clinical use.

Determination of biapenem in human plasma and urine by a simple HPLC method for its pharmacokinetics study

A simple high-performance liquid chromatography （HPLC） method was established and subsequently used to study the pharmacokinetics of biapenem in healthy volunteers. Chromatography separation was carried out using a C18 reverse-phase column with an isocratic mobile phase consisting of 0.05 M ammonium acetate-methanol, either for plasma （94：6, v/v, and flow rate 1.0 mL/min） or for urine samples （97.5：2.5, v/v, flow rate 1.5 mL/min）. The UV detector was set at 300 nm. The assay was linear over the range of 0.25 mg/L-50 mg/L for plasma samples and 0.50 mg/L-200 mg/L for urine samples. The intra-day and inter-day RSD values were lower than 2.8% and 4.6%, respectively, for biapenem in plasma, 2.4% and 2.5%, respectively, for biapenem in urine. Biapenem was stable at room temperature for up to 6 h in plasma and 8 h in urine when MOPS was added immediately after sample collection. An intravenous single dose of 600 mg biapenem was administered to 12 healthy male volunteers. The pharmacokinetic parameters were calculated by Winnonlin with a noncompartment model. The pharmacokinetic parameters were obtained as following： Cmax 37±6 mg/L, t1/2 1.27±0.21 h, AUC0-8h 56±8 mg/L/h, and AUC0-∞57±8 mg/L/h. The accumulated urine excretion rate in 24 h was 58%±5%. The established HPLC method was validated and suitable for the pharmacokinetic study of biapenem.

Preparation of the nanostructured lipid carriers of artemisinin and its pharmacokinetic evaluation

Artemisinin（ART） is a widely used active drug for malaria, including severe and cerebral malaria. However, its therapeutic efficacy is affected by its lower bioavailability. In the present study, nanostructured lipid carriers（NLCs） were proposed as carrier of ART to improve pharmacokinetic properties of the drug. ART-NLC was prepared by high-pressure homogenization based on orthogonal design. The particle size, zeta potential, encapsulation efficiency（EE） and percentage of drug loading（DL） of ART-NLC were（53.06±2.11） nm,（–28.7±3.59） m V, 73.9%±0.5% and 11.23%±0.37%, respectively. ART-NLC showed the sustained release characteristics and scarcely the hemolysis effect on human red blood cells. The pharmacokinetics of ART-NLC for rats after tail intravenous injection（i.v） or intraperitoneal injection（i.p） were investigated by liquid chromatography-tandem mass spectroscopy（LC-MS/MS）. And ART solution was designed as control preparation. For rats of i.v groups, the AUC0–∞（（707.45±145.65） ng·h/m L） of ART-NLC were significantly bigger than that of ART（（368.98±139.58） ng·h/m L）. The MRT（（3.38±0.46） h） of ART-NLC was longer than that of ART（（1.39±0.61） h）. And similar results were observed for rats of i.p groups. The AUC0–∞（（1233.06±235.57） ng·h/m L） and MRT（（4.97±0.69） h） of ART-NLC were both bigger than those of ART, which were（871.17±234.03） ng·h/m L） and（1.75±0.31） h）, respectively. Compared with ART, ART-NLC showed a significant increase in AUC0–∞（P〈0.05） and MRT（P〈0.001） for both i.p and tail i.v administrations.