西红花苷-1经大鼠肌肉注射的体内药动学研究

目的探讨西红花中西红花苷-1经肌肉注射后在大鼠体内的药动学特征。方法大鼠经肌肉注射西红花苷-1后,采用反相高效液相色谱法测定大鼠血浆中西红花苷-1的量,DAS 2.0软件计算各组大鼠西红花苷-1的药动学参数。结果西红花苷-1在大鼠体内的血药浓度经时曲线符合单室模型,主要药动学参数:t1/2a(107±23.18)min,t1/2(160±59.45)min,Tmax(87±29.83)min,Cmax(3.75±0.71)μg/mL,AUC(764±82.05)μg/(min·mL),CL(0.019±0.005)L/(min·kg),V(4.01±1.07)L/kg,MRT(142±23.09)min。结论西红花苷-1肌肉注射后吸收较快,分布广泛,平均体内滞留时间短,为快速处置类药物。     

HPLC测定丹皮中丹皮酚在大鼠体内血药浓度及药动学研究

目的:建立测定大鼠血浆中丹皮酚浓度的HPLC法,并用于丹皮酚注射给药后在大鼠体内的药动学研究。方法:采用水蒸汽蒸馏法提取丹皮中的丹皮酚,大鼠尾静脉注射4 mg.kg-1丹皮酚,于给药后不同时间采集血样,用乙腈处理血浆样品,震荡离心分离上清液用HPLC测定。选用DiamonsilTM钻石C18色谱柱(4.6 mm×250 mm,5μm),流动相甲醇-水(60∶40),流速1.0 mL.min-1,检测波长274 nm,柱温常温,进样量20μL。结果:血浆样品中丹皮酚无干扰,丹皮酚在血浆样品中标准曲线线性范围0.204~20.4 mg.L-1,r=0.999 9。丹皮酚平均回收率92.27%,最低检测浓度为10 mg.L-1,最低定量限LOQ为0.204 mg.L-1,日内、日间RSD4.9%。丹皮酚血药浓度数据用药动学软件kinetica处理,丹皮酚在大鼠体内的血药浓度-时间过程符合二房室模型,AUC=(111.88±14.44)mg.L-1.min-1,MRT=(23.25±5.86)min,Cmax=(8.99±0.84)mg.L-1,Kel=(0.082±0.015)min-1,t1/2 Kel=(8.73±1.54)min。结论:该方法简便、快速、重复性好,适用于丹皮酚大鼠血药浓度测定及药代动力学研究。     

当归腹痛宁滴丸中藁本内酯的测定及大鼠体内的药动学

目的了解市售当归腹痛宁滴丸中藁本内酯的量及口服后藁本内酯在大鼠体内的药动学。方法用气相色谱法测定当归腹痛宁滴丸中藁本内酯的量,SD大鼠灌胃给药,在设定的时间点采血0.3 mL,离心分离血浆,HPLC法测定藁本内酯的血药浓度,计算药动学参数,与藁本内酯静脉注射给药比较,对其在大鼠体内的药动学特征进行评价。结果当归腹痛宁滴丸中藁本内酯的量为0.19 mg/粒。当归腹痛宁滴丸灌胃给药后,藁本内酯25 mg/kg组,其Cmax为(620.395±47.69)μg/L,Tmax0.08 h,AUC(0-∞)(709.346±77.775)μg/L·h,t1/2z(4.331±1.278)h;12.5 mg/kg组Cmax为(173.902±13.654)μg/L,Tmax0.08 h,AUC(0-∞)(365.003±72.813)μg/L·h,t1/2z(2.236±0.188)h;静脉注射藁本内酯25 mg/kg后Cmax(675.965±41.968)μg/L,Tmax0.08 h,AUC(0-∞)(949.501±63.182)μg/L·h,t1/2z(3.085±0.137)h;静脉注射12.5 mg/kg时Cmax(391.402±25.251)μg/L,Tmax0.08 h,AUC(0-∞)(391.078±26.609)μg/L·h,t1/2z(2.985±0.241)h。结论当归腹痛宁滴丸口服,其有效成分藁本内酯胃肠道吸收迅速,生物利用度高,给药后药时曲线呈双吸收峰,可能与滴丸中藁本内酯释放特征有关。     

紫丁香苷在大鼠体内的药动学研究

目的建立反相高效液相色谱法测定大鼠血浆中紫丁香苷并进行药动学研究。方法大鼠血浆样品经甲醇沉淀蛋白,以甲醇-0.5%冰醋酸水溶液(30∶70)为流动相,用Diamonsil C18色谱柱(200 mm×4.6 mm,5μm,Dikma)分离,检测波长为265 nm。结果紫丁香苷的线性范围为0.24～30.00μg/mL。日内、日间精密度RSD小于7.6%,准确度(RE)在±5.5%范围内。提取回收率大于70%。此法应用于大鼠尾静脉注射紫丁香苷(1.35 mg/kg)的药动学研究,AUC(0-t)为(3.26±0.60)μg.h/mL,t1/2为(0.41±0.04)h。结论该方法简便、专属性强,适用于紫丁香苷的药动学研究。     

川芎挥发油中藁本内酯在大鼠体内的药动学研究

目的 测定川芎挥发油中藁本内酯在大鼠体内的药动学.方法 采用RP-HPLC法,以蛇床子素为内标物测定大鼠口服川芎挥发油的β-环糊精包合物后藁本内酯的血药浓度,使用3P97药动学软件计算其药动学参数.结果 藁本内酯在大鼠体内符合二室模型,主要的药动学参数:t_(1/2)(α)为(1.429±1.161)h,t_(1/2)(β)为(6.877±2.275)h,t(peak)为(3.401±1.951)h,AUC为(70.87±25.92)μg/mL·h.结论 以蛇床子素为内标,RP-HPLC法能够准确、灵敏地测定藁本内酯在大鼠体内的药动学.     

大鼠舌下静脉给药华蟾毒配基的药动学研究

目的建立华蟾毒配基在大鼠体内的血药浓度的HPLC测定方法,并根据血药浓度-时间数据计算其体内药动学参数。方法经舌下静脉分别注射0.251、0.503、1.006mg/kg华蟾毒配基,采用RP-HPLC法测定血清中药物浓度,用3P87药动学软件计算药动学参数。结果华蟾毒配基在大鼠体内的动力学过程可用一级动力学过程的二室开放型模型来描述。高、中、低3个不同剂量组的主要药动学参数分别为t1/2α0.4830、0.3777、0.2723h;t1/2β4.4189、5.8972、2.4682h;V(c)2.5120、8.6606、27.9378L/kg;AUC12.1970、8.4123、2.9056μg/(h·mL);CL2.0497、5.9437、34.4166L/(kg.h)。结论本研究建立的RP-HPLC测定大鼠静脉注射不同剂量华蟾毒配基后血药浓度的实验方法简便、快速、灵敏,血清中内源性物质不干扰测定,可为华蟾毒配基临床安全合理用药和制剂质量控制提供依据。     

醋蒸对南五味子木脂素类成分在大鼠体内药代动力学的影响

目的考察醋蒸对南五味子木脂素类化学成分在大鼠体内代谢规律的影响。方法给大鼠灌服相同原药材量的醋蒸前后南五味子提取物,于不同时间点采集血浆样本,采用高效液相色谱法测定不同时间点大鼠血浆样品中五味子酯甲和五味子甲素含量,绘制血药浓度-时间曲线,采用DAS2.0药代动力学分析软件计算药代动力学参数。结果五味子酯甲和五味子甲素在大鼠体内药代动力学模型均符合单房室模型。南五味子醋蒸前后样品中五味子酯甲血药浓度分别在给药后(4.250±1.523)、(5.750±1.784)h达到峰值,实测Cmax分别为(2.197±0.995)、(2.815±0.842)μg/mL,T1/2分别为(2.654±0.377)、(3.504±0.856)h;南五味子醋蒸前后样品中五味子甲素血药浓度分别在给药后(3.250±1.836)、(4.250±1.471)h达到峰值,实测Cmax分别为(1.922±0.773)、(2.307±0.602)μg/mL,T1/2分别为(2.111±1.185)、(3.242±2.126)h。南五味子醋蒸前后在大鼠体内主要药代动力学参数存在差异。结论从五味子酯甲和五味子甲素的药代动力学参数分析,醋制使南五味子木脂素类成分大鼠体内代谢明显减慢。     

四神丸水煎液中补骨脂素和异补骨脂素的大鼠体内药动学研究

目的 建立测定大鼠血清中补骨脂素和异补骨脂素质量浓度的HPLC法,研究四神丸水煎液(补骨脂、肉豆蔻、五味子、吴茱萸和大枣)中补骨脂素和异补骨脂素在大鼠体内的药动学特性.方法 SD大鼠一次性灌胃给予四神丸水煎液,采用HPLC法测定不同时间点血药浓度,应用DAS2.0软件计算药动学参数.结果 补骨脂素和异补骨脂素在血清样品中的标准曲线线性范围分别为0.109 ～21.80 μg/mL(r =0.999 8)、0.097～19.40 μg/mL(r=0.999 2),回收率满足要求,且日内及日间精密度RSD均低于15％.补骨脂素和异补骨脂素在大鼠体内的主要药动学参数分别为:t1/2为(4.28±0.68)、(4.97±1.25)h;Tmax为(8.25±0.71)、(8.25±0.71)h;Cmax为(7.85±0.78)、(3.53±0.62) mg/L;AUC(0 -∞)为(102.10±15.98)、(51.37±8.33) mg·h/L;MRT(0-∞)为(10.65±0.92)、(11.78±1.49)h.结论 该方法简便、快速,适用于补骨脂素和异补骨脂素在大鼠体内的血药浓度测定及药动学研究.     

在大鼠体内小青龙汤对茶碱药动学的影响

目的探讨在大鼠体内小青龙汤对茶碱药动学的影响。方法 12只雄性Wistar大鼠随机分为小青龙汤给药组(灌胃给药1 g·5 ml-1.kg-1·d-1)和生理盐水对照组(5 ml.kg-1·d-1),每组6只,连续给药7 d,于第8天灌胃给药小青龙汤(或生理盐水)后1 h静脉注射氨茶碱(15 mg/kg),并进行采血。采用HPLC分析方法测定大鼠血浆中茶碱浓度,并计算茶碱的药动学参数。结果与生理盐水组比较小青龙汤给药组的茶碱清除率CL显著变小(P<0.05),消除半衰期t1/2和体内滞留时间MRT0→∞,显著延长(P<0.05),而表观分布容积Vz和血药浓度-时间下面积AUC0→∞无显著性差异(P﹥0.05)。生理盐水组和小青龙汤组的茶碱药动学参数分别为:t1/2(5.30±0.89,7.22±1.47)h;CL(0.054±0.008,0.044±0.007)L·h-1;Vz(0.408±0.047,0.452±0.037)L;AUC0→∞(239.99±30.24,287.17±50.11)μg·h-1·ml-1;MRT0→∞(7.16±1.13,9.80±2.14)h。结论在大鼠体内小青龙汤可能抑制茶碱的代谢过程。     

和厚朴酚在大鼠体内药动学及唾液分布研究

目的：探讨和厚朴酚静脉注射给药后在大鼠体内的动态变化规律及其在唾液中的分布情况。方法：大鼠尾静脉注射和厚朴酚,用反相高效液相色谱法测定和厚朴酚在血浆、唾液中的浓度,采用药动学软件3 P97分析数据,确定药动学参数。结果：和厚朴酚在大鼠体内符合二室模型分布,主要药动学参数：t1／2＝（102．980±10．600） min,AUC＝（1219．260±120．520）μg· min／mL,Vc＝（0．722±0．027） L／kg, CL＝（0．0246±0．002）L／min。结论：和厚朴酚可在唾液中检测到,给药后腮腺、颌下腺中的药物浓度与血浆中的药物浓度有一定的相关性。表明腮腺和颌下腺唾液样本将来可被用于和厚朴酚的治疗监测。     

Pharmacokinetic Study of Baicalein and Its Major Metabolites after iv Administration in Dogs

Objective To develop and validate a simple,rapid,sensitive,and reproducible HPLC method for simultaneous determination of baicalein and its metabolite baicalin in dog plasma and for the subsequent pharmacokinetic study after iv administration to dogs.Methods An accurate and reproducible HPLC-UV method was developed and validated for simultaneous determination of baicalein and baicalin in dog plasma,using luteolin as internal standard.The analytes were separated by an Agilent Zorbax SB-C18 column(250 mm × 4.6 mm,5 μm) and the column temperature was maintained at 40 ℃.The mobile phase was a binary mixture of acetonitrile and water(27:73) ,containing 0.05% phosphoric acid in water,with a flow rate of 1.0 mL/min.The UV detector was set at 276 nm.Results Linear relationships were validated over the range of 0.05-25 μg/mL for baicalein and 0.05-20 μg/mL for baicalin.The intra-and inter-day precision values for all samples were within 8.0%,using relative standard deviation.This method was successfully applied to the pharmacokinetic studies in dogs after iv administration of baicalein.Baicalein was converted to baicalin quickly.Cmax values were 21.13 μg/mL at 0.05 h for baicalein and 1.57 μg/mL at 0.5 h for baicalin,areas under the plasma concentration-time curve were 4.97 h·μg/mL for baicalein and 0.63 h·μg/mL for baicalin,and the elimination half-life is 0.50 h for baicalein and 0.75 h for baicalin,respectively.Conclusion The method is able and sufficient to be used in drug metabolism and pharmacokinetic studies of baicalein.     

Pharmacokinetic Study on Hyperoside in Beagle’s Dogs

Objective To develop and validate a simple, rapid, sensitive, and reproducible HPLC method for determination of hyperoside in plasma of dogs and for the subsequent pharmacokinetic (PK) study. Methods An accurate and reproducible HPLC-UV method was developed and validated for the determination of hyperoside in plasma of dogs, using kaempferol as internal standard. The plasma samples of dogs following ig administration of hyperoside were analyzed for the detection of quercetin after enzymatic hydrolysis treatment with combined β-glucuronidase and sulphatase. The analytes were separated on a Diamonsil C 18 column (250 mm × 4.6 mm, 5 μm). The mobile phase consisted of methanol-buffer solution (0.1 mol/L NH 4 Ac + 0.3 mmol/L EDTA-Na 2 )-acetic acid (60:40:1) and was delivered at a flow rate of 1 mL/min. The UV detector was set at 370 nm and the column temperature was maintained at 35 ℃. The sample injection volume was 20 μL. Data were collected and analyzed using the ANASTAR software. PK parameters were calculated with DAS software (2.0). Results Linear relationships were validated over the range of 0.01-1 μg/mL for hyperoside (r = 0.9997). The intra- and inter-day precision values for all samples were within 10.0%, and the accuracies of intra- and inter-day assays were within the range of 92.4%-102.4%. The validated method was successfully used to determine the hyperoside concentration in plasma of dogs for up to 12 h, after a single ig administration (25 mg/kg). The mean PK parameters for male and female dogs were as follows: C max (0.18 ± 0.05) and (0.16 ± 0.05) μg/mL, AUC 0-∞ (0.79 ± 0.34) and (0.86 ± 0.27) μg/(mL·h), t 1/2(ka) (0.89 ± 0.41) and (0.88 ± 0.28) h, respectively. Statistical analysis on the PK of hyperoside in male and female groups showed that sex had no significant impact on the PK of hyperoside (P > 0.05). Conclusion The method is able and sufficient to be used in drug PK studies of hyperoside.     

马钱子碱聚乳酸纳米粒在家兔体内的药动学研究

目的 研究马钱子碱聚乳酸纳米粒(Bru-PLA-NPs)iv注射给药后在家兔体内的药动学行为.方法 建立HPLC法测定家兔血浆中马钱子碱浓度.色谱柱为Kromasil C_(18)(250 mm×4.6 mm,5μm);流动相为乙腈-水(23∶77),水中含庚烷磺酸钠1.01 g/L,磷酸二氢钾1.36 g/L,加磷酸调节pH至2.8;体积流量为1 mL/min;检测波长为265 nm;柱温为25℃.采用3p87软件计算马钱子碱药动学参数.结果 单剂量iv Bru-PLA-NPs(4 mg/kg)后马钱子碱在兔体内的药动力学数据符合三室模型,单剂量静注马钱子碱溶液(4 mg/kg)后符合二室模型;与马钱子碱溶液相比,Bru-PLA-NPs给药后,马钱子碱的消除半衰期(t_(1/2β))提高6.6倍;生物利用度提高8.7倍.结论 与马钱子碱溶液相比,Bru-PLA-NPs iv给药后马钱子碱在家兔体内的药动学行为发生了显著变化.     

Determination of Shionone in Rat Plasma by HPLC and its Pharmacokinetic study

Objective To develop a sensitive,simple,and accurate method for the determination of shionone in rat plasma after ig administration of Asteris Radix petroleum ether extract(RAPE).Methods The separation was achieved by HPLC on a RP18 column(150 mm × 3.9 mm,5 μm) with a mobile phase composed of acetonitrile-0.05% phosphoric acid water(98:2) at a flow rate of 1.0 mL/min.UV Detector was set at 200 nm and friedelin was chosen as an internal standard.Results The linear range of the standard curves was(0.3443-22.0...     

Validated LC- MS/MS assay for the determination of wogonin: Application to a preclinical pharmacokinetics and bioavailability of different wogonin administration in beagle dogs

Objective To develop an LC-MS/MS method for determining the concentration of wogonin in dog plasma and investigate the pharmacokinetics and bioavailability by different administrations of wogonin in Beagle’s dogs.Methods LC-MS/MS was employed in determining the concentration of wogonin with the selected ion monitoring model after liquid-liquid extraction with ethyl acetate of dog plasma samples.The lower limit of quantification was 0.105 μg/L.Target ions were at m/z 285.0→270.0 for wogonin and 373.3→305.3 for finasteride.In a randomized,self-control,and cross-over study,six male Beagle’s dogs were treated with different administration methods in three test periods.Pharmacokinetic parameters were calculated with DAS software(Ver.2.0).Results The calibration curve was linear in the range of 0.105-107.36 μg/L for wogonin in dog plasma samples.The main pharmacokinetic parameters of ig administration(native drug of 15 mg/kg and solution preparation of 5 mg/kg) and iv route were as follows:Cmax(2.5 ± 1.1),(7.9 ± 3.3),and(6838.7 ± 1322.1) μg/L,tmax(0.7 ± 0.3) and(0.3 ± 0.2) h for the both former,AUC0-t(7.1 ± 2.0),(21.0 ± 3.2),and(629.7 ± 111.8) μg.h/L.The absolute bioavailability of native and solution of wogonin were(0.59 ± 0.35)% and(3.65 ± 2.00)%,respectively.Conclusion The validated method is convenient,sensitive,and specific,and the improvement of wogonin solubility could remarkably increase the absolute bioavailability.     

类风湿关节炎患者雷公藤甲素血清浓度测定及其药动学研究

目的建立雷公藤甲素血药浓度的超高效液相色谱检测法,并对类风湿关节炎患者口服雷公藤多苷片后雷公藤甲素的体内药代动力学进行初步探讨。方法入组3例类风湿关节炎患者,其血清以艾司唑仑为内标,用乙酸乙酯进行提取后进样测定。色谱柱为Waters Acquity C18柱(2.1 mm×100 mm,1.7μm),流动相为乙腈-0.1%冰乙酸(30∶70),流速为0.2 mL/min,柱温为30℃,检测波长为220 nm。血药浓度数据用DAS2.1.1药动学计算机程序处理。结果雷公藤甲素与内标物分离良好,保留时间分别为4.9、8.9 min左右。雷公藤甲素血药浓度在13.13~840.00 ng/mL范围内,峰面积与内标物峰面积比值之间的线性关系良好,日内、日间精密度均RSD15%,回收率为88.25%~99.33%。雷公藤甲素药动学参数Cmax、Tmax、T1/2β、AUC0-12 h分别为(159.97±42.43)ng/mL、(1.33±0.58)h、(7.51±2.26)h、(1131.12±89.20)mg?h/L。结论雷公藤甲素药动学符合二室模型,吸收迅速,个体之间存在差异。     

HPLC-UV法测定大鼠血中[6]-姜酚的浓度

目的建立测定大鼠血浆中[6]-姜酚浓度的HPLC-UV法,为进一步研究[6]-姜酚的药代动力学提供可靠的方法。方法大鼠血浆样品以液-液萃取法提取后,采用HPLC-UV测定大鼠血浆中[6]-姜酚的浓度。HPLC条件:Hypersil C18柱(250mm×4.6mm,5μm),乙腈-水(45:55)为流动相,进样量:20μL,流速:1.0mL/min,紫外检测波长:280nm。结果[6]-姜酚线性范围为0.25～5.0μg/mL,最低检测限为0.1μg/mL,日内精密度RSD5.5%,日间精密度RSD6.8%。结论该测定方法具有灵敏、专一和快速的优点,可用于测定大鼠灌胃给药后[6]-姜酚的血浆浓度。     

高效液相色谱-荧光光谱法测定大鼠血浆中葛根素及其药动学研究

目的建立高效液相色谱-荧光光谱法测定大鼠血浆中葛根素含量。方法色谱柱选用Hypersil ODS柱,流动相为甲醇∶水(含50 mmol/L醋酸铵)=23∶77(V/V),流速为1 mL/min,荧光检测器参数:激发波长250 nm,发射波长480 nm,增益为11,柱温30℃。结果该方法专属性强,在0.16~120 mg/L浓度范围内线性关系良好,最低检测限为10μg/L,准确度介于99%~104%,日间、日内精密度均小于10%。该方法成功应用于大鼠静脉注射葛根素的药动学研究中,葛根素在大鼠体内符合开放二房室模型,主要的药动学参数如下:AUC0→t(41.94±12.90)mg/(L.h),AUC0→∞(44.37±28.90)mg/(L.h),MRT(0.97±0.37)h,T1/2(1.06±0.39)h,Vss(0.09±0.02)L,Vz(0.14±0.03)L,Cl(0.10±0.05)L/h。结论本方法无需柱后修饰,简单、可靠,适于大鼠血浆中葛根素的检测。