Objective To develop a sensitive and specific method for the determination of candesartan in human serum and to study the pharmacokinetics characteristics of candesartan cilexetil tablets in Chinese healthy volunteers using this method. Methods The samples were extracted from serum with diethyl ether. Chromatography was performed on an YMC ODS column (250 mm×4.6 mm i.d., 5 μm) with a mobile phase consisting of 10 mmol/L potassium dihydrogen phosphate (adjusted to pH 3.0 with phosphoric acid) and acetonitrile (60∶40, V/V) at a flow rate of 1.0 mL/min. Quantification was performed by fluorescence detection at an excitation wavelength of 270 nm and an emission wavelength of 390 nm. A single oral dose of 8mg candesartan cilexetil tablet was given to 20 healthy volunteers. The candesartan concentrations in serum were determined by the above-mentioned method. The main pharmacokinetic parameters were detected and calculated. Results The linear range of candesartan concentration was 1.01 to 202 μg/L in serum with a correlation coefficient (r) of 0.999 7. The relative standard deviations (RSDs) of intra-day and inter-day assays were 5.22%-9.14% and 3.58%-10.39%, respectively. Conclusions This method proved to be sensitive and reproducible for pharmacokinetic studies of candesartan cilexetil in healthy volunteers after a single oral administration (8 mg).

AIM:To establish a rapid HPLC method for determination of acetaminophen and pamabrom in compound acetaminophen and pamabrom tablets in human plasma.METHODS:The samples were extracted from plasma with ethyl acetate in hydrochloric acid surroundings.Chromatograph was carried out on a Diamon- sil~(TM)C_(18)column,using theophylline as internal standard,and the concentrations of acetaminophen and pamabrom were determined simultaneously.The mobile phase was 0.2% trifluoroacetic acid-acetonitrile(87:13,V/V), the detection wavelength was set as follows:0.00-8.00 min:249nm,8.01-13.00min:278nm.RE- SULTS:The retention time of acetaminophen and pamabrom were approximately 5.9 min and 11.3 min,respec- tively.A good linearity was shown in the concentration range 0.02-20 mg·L~(-1)for both constituents.The extrac- tion recovery was more than 60%(n=5)and the method recovery was more than 70%(n=5).The interday or intraday precision was less than 7.5% in replicate analysis(n=5).CONCLUSION:This HPLC method is simple,quick,sensitive and accurate.It is suitable for clinical pharmacokinetic or bioequivalence study of compound acetaminophen and pamabrom tablets.

AIM To study the pharmacokinetics and relative bioavailability and evaluate the bioequivalence of two roxithromycin capsules.METHODS A single oral dose of 300 mg roxithromycin of test capsule and reference one was given to 20 healthy volunteers respectively in 2 divided groups in a double cross-over,controlled study.The roxithromycin concentrations in plasma were determined by HPLC method.RESULTS The ρmax,tmax,t12,AUC0→t and AUC0→∞ of test roxithromycin capsule and reference one were(8.71±3.07) mg·L-1 and (8.74±3.66) mg·L-1,(1.68±0.59) h and(1.75±0.34) h,(14.46±3.55)h and(14.30±2.82) h,(101.91±38.34) mg·h·L-1 and(100.52±36.91) mg·h·L-1,(111.60±40.16) mg·h·L-1 and(109.79±37.85) mg·h·L-1,respectively.CONCLUSION The results of statistical analysis show that two formulations are bioequivalent.

A sensitive and specific method for the determination of bifendate in human plasma was developed, based on high-performance liquid chromatography (HPLC)–mass spectrometry (MS). The samples were extracted from plasma with diethyl ether, followed by separation and evaporation after addition of internal standard diazepam. The residue was reconstituted in methanol and injected into the HPLC–MS. Chromatography was performed on an Inertsil ODS column with a mobile phase consisting of methanol–distilled water (70/30, v/v) at a flow rate of 0.3mL/min. Quantitative analysis was achieved by MS detection, using a mass spectrometer equipped with an electrospray ionization interface (ESI) and operated in selected ion monitoring (SIM) and positive-ionization mode using target ions at m/z 419 for bifendate and m/z 285 for internal standard, respectively. The linearity was confirmed in the concentration range of 2–200ng/mL in human plasma and the precision of this assay was not more than 6.79% over the entire concentration range. The method was sensitive and repeatable enough to be used in pharmacokinetic and bioavailability studies.

AIM: To develop a high-performance liquid chromatography-mass spectrometry (HPLC-MS) method for the determination of lovastatin concentration in human plasma. METHODS: The chromatographic separation was performed on a Diamonsil C_ 18 column (5 μm, 2.1 mm×150 mm) at 40 ℃. The mobile phase, a mixture of acetonitrile ∶water (60 ∶40), was delivered at a flow-rate of 0.4 mL·min -1. MS detection in single ion monitoring mode (SIM) using electrospray ionization (ESI) as an interface was applied to determine positive ions at m/z 405 for lovastatin and m/z 419 for internal standard (IS, simvastatin). Lovastatin and IS were isolated by a liquid-liquid extraction using cyclohexane: methylene dichloride (3 ∶1) as the solvent. RESULTS: High specificity and a low quantitation limit (0.1 μg·L -1) were achieved. Linearity was confirmed in the concentration range of 0.5-50 μg·L -1 with the correlation coefficient (r)=0.998 9. The relative standard deviation (RSD) values of intra- and inter-day assay were less than 14.47 % and the recoveries were within 88.12 %-112.09 %. The extraction recovery of lovastatin was ranged from 76.28 % to 77.15 %. CONCLUSION: HPLC-MS method is sensitive, specific and applicable to pharmacokinetic studies of lovastatin in human.

Purpose To study the pharmacokinetics characteristics of pazufloxacin in healthy volunteers. Methods Totally 36 healthy adult male volunteers participated in this 3 dosages experiment (150,300,600 mg,12 volunteers/group). The volunteers were randomly assigned to 3 treatment groups and were given respectively the dose of 150,300,600 mg by means of intravenous infusion. Serum was separated and the concentration of pazufloxacin in human serum was determined by HPLC using fluorescence detector after protein had been deposited. The values of c_ max and t_ max were directly detected, and AUC was calculated by linear trapezoid method. Results The main pharmacokinetic parameters of pazufloxacin of 3 dosages(150,300,600 mg) were as follow: AUC_ 0～t (μg·h·mL -1 ) were 7.66±1.65,14.92±3.75,29.88± 4.66 respectively;AUC_ 0～∞ (μg·h·mL -1 ) were 8.19±1.73,15.42±3.73,30.55±4.83 respectively;c_ max (μg·mL -1 )were 3.55±1.21,8.16±2.51,17.38±5.42 respectively;t_ 1/2 (h)were 2.52±0.16 , 2.18±0.18 ,2.12±0.13 respectively;K_e(h -1 ) were 0.28±0.02,0.32±0.03,0.34±0.03 respectively;V(L) were 40.95±6.05,40.27±9.95,36.50±4.98 respectively;Cl(mg/h) were 11.51±1.90,12.88± 2.85 ,12.34±2.14 respectively;MRT(h) were 2.77±0.23,2.43±0.21,2.45±0.23 respectively;t_ max of pazufloxacin was 0.5 hr for all of these 3 dosages. Conclusions No significant differences in pharmacokinetic parameters, such as t_ max , t_ 1/2 , K_e, V, Cl, MRT, AUC_ 0～t /dose,AUC_ 0～∞ /dose and c_ max /dose are shown among the three dose groups,and a linear pharmacokinetic is featured.

AIM:To study the pharmacokinetics characteristics of minocyline and provide the evidence for proper clinical application METHODS: Eight healthy male volunteers participated in this trail and were giv en minocyline by means of intravenous infusion in a single (200 mg) and multiple (100 mg,bid× 5 d ) doses.A HPLC method was applied to determine the serum dr ug c o ncentrations and calculate the pharmacokinetic parameters. RESULTS: The pharmacokinetic parameters obtained from the single-dose study w ere as follows:c_ max =(5.4±s 0.9) mg·L -1 ;t_ max = 2 h ; t_ 1/2 :(26±3) h;MRT=(36±5) h;AUC_ 0-72 = (94±24) mg· h ·L  -1 ;AUC_ 0-∞ =(109±29) mg· h· L -1 .The steady-state pha rmac okinetic parameters after giving multiple doses were:c ss _ max =(8.4 ±1.5) mg·L -1 ;c ss _ min =(1.0±0.4) mg·L -1 ; c ss _ av =(2.1± 0.6) mg·L -1 ;AUC SS =(149± 42) mg ·h·L -1 ;DF= 3.7±0.6 . CONCLUSION: The main pharmacokinetic parameters of minocyline are consistent with those hav e been reported previously.

目的:建立一种测定甲磺酸多沙唑嗪片剂的HLPC法,并用该方法测定甲磺酸多沙唑嗪片剂含量、含量均匀度和溶出度.方法:色谱柱为Dikma C18(150 mm×4.6 mm,5μm),流动相:甲醇-醋酸缓冲液(52:48,V/V);检测波长250 nm;柱温30℃.结果:甲磺酸多沙唑嗪对照品溶液的线性方程为A=60.724 c+1.941(n=7,r=1.000,线性范围0.5～50 mg·L-1),日内、日间RSD均＜2％,检测限为2.5ng(rSN=3).甲磺酸多沙唑嗪片剂含量在101％～104％之间,3批片剂45min平均溶出度在84％～87％之间,含量均匀度A+1.8S＜15.结论:此法适用于甲磺酸多沙唑嗪片剂含量和溶出度测定.

AIM: To establish a simple and rapid method for determining mycophenolic acid (MPA) in human plasma. METHODS: The plasma concentration was determined by HPLC, and the detector wavelength was set at 303 nm. The plasma sample purification was limited to protein precipitation with acetonitrile (containing 0.1 mol·L -1 phosphoric acid). The sample was separated on an AgilentXDB C 18 column (150 mm×4.6 mm,5 μm),the mobile phase consisted of sodium acetate(30 moL·L -1,pH 3.0) and acetonitrile (57∶43, V/V). The flow rate was 1.0 mL·min -1. RESULTS: The calibration curve of MPA was linear in the range of 0.6-30 mg·L -1(r=0.9995,n=6) in plasma. The limit of detection for MPA was 0.2 mg·L -1. The method recovery rate of low, medium and high concentrations of MPA was (98.9±1.5)%. The extract recovery rate was (106.73±0.27)%. The inter-day RSD of precision was 1.58 %, 0.93 % and 0.65 %. The intra-day RSD of precision was 4.61 %, 1.03 % and 5.66 %. CONCLUSION: HPLC is a simple, rapid, reliable quantitative method for pharmacokinetic study and monitor of MPA.

AIM: To compare the pharmacokinetic parameters of the two kinds of omeprazole capsules, following per oral administration. METHODS: Twenty healthy volunteers were per orally cross-administrated two kinds of omeprazole two capsules (20 mg omeprazole per capsule). The plasma concentrations of omeprazole were determined by the reverse phase high performance liquid chromatography (RP-HPLC) method. The pharmacokinetic parameters of two capsules preparations were calculated and compared by 3P97 Software. RESULTS: The concentration-time curve of omeprazole complied with the single compartment model. Following per oral administration of omeprazole 40 mg, there were no statistical significant differences of the main pharmacokinetic parameters between the two capsules preparations by the analysis of variance (P0.05). The relative biological availabilities of the two capsules preparations were (95.5-110.7) %. CONCLUSION: The results demonstrate that the two kinds of omeprazole capsules are bioequivalent.

AIM: To evaluate the quality of three marketed isosorbide nitrate intravenous injections. (Isosorbide dinitrate from Zhuhai Schwarz Pharma.,Shandong Qilu Pharma., and isosorbide mononitrate from Shandong Lunan Pharma.) METHODS: HPLC, GC, and freezing point depression methods were used to examine the qualities of three isosorbide nitrate intravenous injections. RESULTS:While few differences existed in the assays of the three brands, there was great difference in osmolarities of three products:the product from Zhuhai Schwarz Pharma.was isotonic (289 mmol·L -1 ), but the other two products were both hyperosmotic (2000 mmol·L -1 ). After analysis by HPLC and GC MS, 1,2 propanediol was found to exist in both injections at concentrations ranged from 23 % to 28 % (kg·L -1 ), and 17 % to 23 % (kg·L -1 ), which led to an abnormal high osmolarity. CONCLUSION:It indicate that all three brands are confirmed with their own product standards, but great difference exists in osmotic pressures of three products, due to 1,2 propanediol containing in two of three products.

AIM: To study the pharmacokinetics of isosorbide mononitrate (ISMN) sustained release capsules (Schwarz product) which produced by Zhuhai Schwarz Pharma Co Ltd, using two ISMN sustained release preparations produced by German Maklo Pharma Co Ltd and Swiss Astla pharma Co Ltd as standard references. METHODS: The plasma concentration of ISMN was determined with gas chromatography method with 4 nitrobengyl acetomitrile as the internal standard. The kinetic parameters were calculated. The linear range of the method is 10-100 μg·L -1 ; the rate of recovery: (100±3)%; the precision of the method, RSD2.3%. RESULTS: There was no statistical significant difference between Schwarz product and Reference 1 on AUC, C max , T 1/2 , MRT and MAT( P 0.05), but significant differences on C 10min , C 20min , C 30min , C 45min , C 60min , T max and T lag ( P 0.05) were observed. There was no statistical significant difference between Schwarz product and Reference 2 on AUC, C max , T max , T 1/2 , T lag and MAT ( P 0.05), but significant differences on MRT, C 20min C 30min ( P 0.05) were obseved. CONCLUSION: The absorption of Schwarz product is much faster than both of the two references.

AIM: To evaluate the bioequivalence of domestic and imported anastrozole tablet. METHODS: According to the crossover design, each volunteer was orally given anastrozole tablets (1 mg). GC determined the drug concertrations in plasma. The linear ranges was from 0.5 to 200.0 μg*L-1 plasma (r=0.9997, n=9). The recovery rates of lower, mid, higher concentration (1.0,10.0,20.0 μg*L-1 plasma were 93.50 %, 100.17 %,98.96 % respectively. Inter-day and intra-day precisions of the method were <13 %. RESULTS: The pharmacokinetic parameters of the domestic and imported tablet were 1.2 h±0.5 h and 1.3 h±0.4 h for T max, 10 μg*L-1±3 μg*L-1 and 10.2 μg*L-1±2.5 μg*L-1 for Cmax, 386 μg*L-1±117 μg*L-1 and 385 μg*L-1±117 μg*h-1*L-1 for AUC0-T,36 h±14 h and 32 h±10 h for T1/2 respectively. The relative bioavailability of the domestic tablet was (100±9) %. CONCLUSION: Domestic and imported anastrozole tablet are bioequivalence in healthy volunteers.

目的:研究3种亚叶酸钙制剂(国产片剂、胶囊和进口片剂)在12名健康志愿者体内的相对生物利用度.方法:同体交叉试验后,测定血浆中亚叶酸钙浓度,计算主要药物动力学参数和相对生物利用度,并进行统计学分析.结果:国产片、胶囊和进口片单剂量75 mg,po后,Tmax分别为(2.5± s 0.3) h,(2.5±0.3) h和(2.4±0.3) h;Cmax为(654±146) μg·L-1,(599±132) μg·L-1和(640±163) μg·L-1;AUC0～∞为(7811±1481) μg·h·L-1,(7091±1397) μg·h·L-1和(7898±1855) μg·h·L-1;T(1)/(2)为(8.7±0.6) h,(8.6±0.4) h和(8.6±0.5) h.国产片、胶囊相对生物利用度分别为(101±14)%,(93±11)%.结论:3种制剂生物等效.

目的:研究国产和进口亚叶酸钙片在12名健康志愿者体内的相对生物利用度.方法:同体交叉试验后,血样采用固相萃取后经RP-HPLC法测定血浆中亚叶酸钙的浓度,计算两种片剂的主要药物动力学参数和相对生物利用度,并进行统计学分析.结果:国产片和进口片单剂量po后,tmax分别为(2.4±0.3)和(2.3±0.3) h,cmax分别为(720±96)和(720±109.9) ng/ml,AUC0→t分别为( 6 382.3± 1 234.1)和( 6 287.7± 1 079.4) ng*h/ml,AUC0→∞分别为( 7 398.8± 1 331.5)和( 7 263.5± 1 225.3) ng*h/ml,MRT0→t分别为(5.88±0.17)和(5.84±0.31) h,T1/2分别为(8.69±1.09)和(8.40±1.21) h.国产片平均相对生物利用度为(101.7±9.6)%.结论:两种片剂在健康志愿者体内为生物等效.