溴泰君(W198)在大鼠和比格狗体内的药代动力学

目的研究溴泰君(W198)在大鼠和比格狗的药代动力学。方法采用HPLC紫外检测方法测定大鼠及比格狗注射W198后血清药物浓度。结果大鼠iv W198 10,20和40 mg·kg^-1 3个剂量的T_1/2β分别为6.60,7.36和6.77 h,AUC_0-24h分别为3.797,7.371和15.192 mg·h·L^-1,V_d分别为7.14,4.33和4.13 L·kg^-1,CL分别为2.83,2.60和2.71 L·(kg·h)^-1。大鼠im W198 20 mg·kg^-1后T_1/2β为11.61 h,AUC_0-24h为4.191 mg·h·L^-1,im的生物利用度为56.9%。比格狗iv W198 5 mg·kg^-1,T_1/2β为11.72 h,AUC_0-24h为12.646 mg·h·L^-1,V_d为0.70 L·kg^-1,CL为0.46 L·(kg·h)^-1。W198与人血浆蛋白的结合率平均为78.0%。结论W198 im的T_1/2β比iv的略长,其生物利用度为56.9%。在10～40 mg·kg^-1剂量内的吸收呈现一级动力学特征。     

线性降解程序变湿法研究青霉素钾的稳定性

报道了一种新的研究湿度对固体药物稳定性影响的试验方法——线性降解程序变湿法。按照这一变湿规律进行程序变湿药物稳定性试验能最大限度地使药物在高湿和低湿范围内降解程度一致，提高了试验的精密度。作者以青霉素钾为模型药物，采用线性降解程序变湿法和指数程序变温法进行试验，求得了E_a，m，A和t_0.9等动力学参数。结果表明，新方法测定结果的精密度明显优于文献报道的程序变湿变温法。     

蝙蝠葛酚性碱对离体大鼠心肌顿抑的保护作用

目的　探讨蝙蝠葛酚性碱(PAMD)对离体大鼠心肌顿抑的作用。方法　采用缺血10min后再灌注30min造成心肌顿抑模型(S) ,灌流液中加0.5mg·mL^-1 PAMD(P)组同样缺血再灌注。结果　灌注末S组LVSP ,+dp/dt_max和-dp/dt_max分别降至预灌末的49% ,53%和58% ,LVEDP则增至422% ;心肌钙含量为(514±142 ) μg·g^-1 (干重) ;出现可逆性心肌超微结构损伤。而P组再灌注末LVSP ,LVEDP ,+dp/dt_max和-dp/dt_max恢复为预灌末值的70% ,205% ,78%和79% ;心肌钙为(316±84) μg·g^-1 (干重) ;以上变化均有显著差异。结论　PAMD对离体大鼠顿抑心肌有保护作用     

3H羟基斑蝥胺的药物代谢动力学研究

将氚标记的羟基斑蝥胺在大鼠体内研究了药物代谢动力学。所得血药浓度-时间数据依一定程序在709电子计算机上拟合曲线,并计算有关参数。结果表明,静脉注射后符合二房室开放型模型,其药代动力学参数为:t1/2α0.067hr,t1/2β2.208hr,V_d(面积)1.237l/kg,V₁0.264l/kg,K_el1.470 hr^-1,清除率0.388l/hr/kg。灌胃后可以单室开放型模型描述,其药代动力学参数为:K_α2.990hr^-1,K_el0.257hr^-1,V_d1.603l/kg,t1/22.693hr,t_max0.90hr,C_max0.745μg/ml,F94.15%。尚将本药以静脉和灌胃两种途径给药后直接观察在大鼠体内的组织分布和在尿粪胆汁中的排泄,结果表明本药分布广,主要经肾排泄,且排泄较快,与药代动力学分析结果相一致。     

25%抗坏血酸注射液稳定性的研究——Ⅰ.25%抗坏血酸注射液变色规律的探讨

探讨了25%抗坏血酸注射液在不同温度下(98、90、80和70℃)含不同抗氧剂的两种处方的绝氧降解变色规律。同时以5%的注射液的一个处方在98℃进行对照。结果表明,抗坏血酸注射液的变色规律可表示为下列回归方程:T_o为注射液的原始透光率,T_o为时间t_o时的透光率,T为时间t时的透光率,t_o和t₁分别为透光率下降到50%左右和接近于0%的时间。k和k′为与变色速度有关的回归系数。此方程代表反S形曲线。在曲线的上半段,m近似为2,故回归方程为:其近似式为:T=T_o-T_okt²=T_o-kt²抗坏血酸注射液的变色速度方程为:变色速度受注射液浓度、抗氧剂种类以及温度的影响。     

蛇床子素在兔体内药物代谢动力学

目的研究蛇床子素在兔体内的药物代谢动力学。方法用高效液相色谱法,以丹皮酚为内标,以甲醇-水(80∶20)为流动相,测定兔血液中蛇床子素(iv,10 mg·kg^-1)的含量。采用3P87程序计算药物代谢动力学参数。结果蛇床子素iv药代动力学符合二房室开放模型,T_1/2α=5.81 min,T_1/2β=42.2 min,K21=0.036 0·min^-1,K₁₂=0.045 0·min^-1,K₁₀=0.054 0·min^-1,AUC=235 mg·min·L^-1,CLs=0.043 0 L·min^-1·kg^-1,V_C=0.780 L·kg^-1。结论蛇床子素在兔体内分布及消除较快     

rasH2转基因小鼠与C57BL/6小鼠单次灌胃F3SM动力学参数比较

目的 比较C57BL/6小鼠(简称C57小鼠)和rasH2转基因小鼠(Tg rasH2小鼠)单次给予相同剂量受试药物F3SM后, 代谢动力学参数的差异, 观察两种动物对于F3SM的代谢动力学的一致性。方法 选用相同周龄的C57小鼠和Tg rasH2小鼠各4只, ig给予相同剂量(60 mg/kg)的F3SM羧甲基纤维素钠溶液。在给药后5、15、30 min及1、3、10、24 h各时间点进行采血, 采血量≥40 μL, 从血样中分离出10 μL血浆, 采用LC-MS/MS方法对样品的药物浓度进行检测, 用软件计算得出AUC_(0-t)、MRT_(0-t)、t_1/2、T_max和C_max, 用配对t检验进行差异性分析。结果 对C57小鼠和rasH2转基因小鼠的AUC_(0-t)、MRT_(0-t)、t_1/2、T_max和C_max进行配对t检验, 显示差异无显著性;二者药时曲线也大致相近。结论 单次给药后, C57小鼠和Tg rasH2小鼠对药物F3SM的代谢特征无显著差异, 提示C57小鼠与Tg rasH2小鼠对本药物的代谢特征相似, 提示在开展Tg rasH2小鼠研究中, 可首先采用C57小鼠进行毒性预探研究.     

普卢利沙星片的健康人体药动学

目的 健康志愿受试者口服普卢利沙星片后,测定血浆中其活性代谢物(UFX)并作药动学研究。方法 10名受试者分别单剂量和多剂量稳态时服用普卢利沙星片(相当于200 mg UFX),采集血浆和尿液样品,液相色谱分离荧光检测UFX浓度,3P97软件计算药动学参数。结果 单剂量时测得UFX的主要药动学参数分别为c_max(1.64±0.29)μg·ml^-1,t_max(0.7±0.2)h,AUC_0-36(6.87±1.78)h·μg·ml^-1,AUC_0-∞(7.14±1.79)h·μg·ml^-1,t_1/2(7.54±0.59)h,MRT(8.76±0.65)h;0～36 h尿液累积排泄量为(56.85±9.12)%。稳态时测得UFX的主要药动学参数分别为c_max(1.26±0.41)μg·ml^-1,t_max(0.8±0.3)h,AUC_0-36(7.77±2.73)h·μg·ml^-1,AUC_0-∞(8.10±2.70)h·μg·ml^-1,t_1/2(7.71±1.13)h,MRT(9.85±1.40)h。结论 健康志愿受试者口服普卢利沙星片后,在体内转化为活性代谢物(UFX)发挥作用,主要经尿液排泄。每日2次,每次2片(相当于200mg UFX),在体内无积蓄。男女健康受试者的主要药动学参数无显著性差异。     

片剂释放度研究——四种测定方法的比较

本实验收集了国内阿司匹林生产样品五种及原料一种,作为典型药品进行了四种方法(杯法,崩解仪法,转篮法及循环法)的体外测定并测定了体内狗血药水平,将体内外测定结果进行了统计分析。以T₅₀%(中位数时间),T_d(特征时间63.2%)及m(斜率)三个参数和体内的T_max(高峰时间),C_max(高峰浓度)及血药水平时间曲线下面积A_uc三个参数作F检验,认为在各方法之间有显著性差异,并且循环法的灵敏性较好,但变异系数以杯法最小,体内外有一定的相关。     

肝靶向米托蒽醌白蛋白微球的研究

用乳化—热固化法制备了米托蒽醌白蛋白微球,并对其形态、大小及其分布、微粉学性质、载药性能、体外释药、稳定性和体内分布进行了研究。结果表明,该载药微球的平均算术径为0.99μm,平均表面径为1.24μm,平均容积径为1.44μm;表观载药量为2.558%±0.101%;有效载药量为1.503%±0.127%;包封率为92.82%±4.60%;体外释药符合双相动力学规律,释药方程为1-Q=0.6428e^-0.2132t+0.3988e^-000150t(γ₁=-0.9951,γ₂=-0.9982);T_1/2α=3.250h,T_1/2β=461.7h;室温放置3个月,微球形态、药物含量等均无明显变化。HPLC测定表明,小鼠尾iv该微球20min内即有77.6%±1.38%的药物浓集于肝脏,具有明显的肝靶向性。提示米托蒽醌白蛋白微球有可能提高米托蒽醌的抗肝癌效果和降低其全身毒副作用。     

Dose-Time-Response Cumulative Multinomial Generalized Linear Model

In toxicological and pharmaceutical experiments, a type of quantal bioassay experiment is designed in which a response, such as mortality, in a group of animals is recorded over time points under different dose levels in the course of the experiment. The application of the typical logit and probit analyses is no longer valid in this situation because it neglects the dependency on time and also the possible interaction of time and dose concentration on the response in the experiment. In this paper, a dose–time-response model is proposed for this type of experiment and a cumulative multinomial generalized linear model that incorporates time and the other experimental conditions as covariates is developed by the theory of maximum likelihood estimation. Both the point estimator and confidence bands for ED₅₀ (t), the concentration of a toxicant that will kill 50% of the animals by a specific time, t; as well as LT₅₀ (d), the time to 50% mortalities for a specific concentration, d, is then formulated in closed form from the newly proposed dose-time-response model. Finally, the newly proposed model is considered for a real data set to demonstrate the application.     

Disposition kinetics in dogs of diethyldithiocarbamate,a metabolite of disulfiram

Following the intravenous infusion of sodium diethyldithiocarbamate to dogs, the disposition kinetics of diethyldithiocarbamate (DDC), a metabolite of disulfiram, were assessed. Approximately 27% of the administered dose was S-methylated, this process exhibiting a mean first-order rate constant of 0. 0569 min^–1 (t_1/2=12.2 min), while the remainder was eliminated by other routes having a rate constant of 0.148 min^–1 (t_1/2=4.68 min). The methyl diethyldithiocarbamate (MeDDC) formed from DDC showed an elimination rate constant of 0.0141 min^–1 (t_1/2=49.2 min). These observations are discussed in the light of previous investigations where the presence of MeDDC has rarely been sought or reported. A few comparisons with prior studies, in which DDC or disulfiram was administered, are made by retrospective kinetic evaluation of published data. The results are discussed in relation to the duration of action of disulfiram in man.Glossary A plasma concentration intercept at the cessation of infusion (mass/volume) - A _T simplifying constant (mass/volume/time) - AUC _M area under the plasma concentration-time curve for MeDDC (mass × time/volume) - b time variable; equalst during infusion, equalsT after the cessation of infusion - B plasma concentration intercept at the cessation of infusion (mass/volume) - B _T simplifying constant (mass/volume/time) - C _D plasma concentration of DDC at any timet (mass/volume) - C _M plasma concentration of MeDDC, expressed as DDC, at any timet (mass/volume) - C _T plasma concentration of total DDC, expressed as DDC, at any timet;C _T=C_D+C_M (mass/volume) - C _t plasma concentration of total DDC, expressed as DDC, at any timet (mass/volume) - Cl _D total body clearance of DDC (volume/time) - Cl _M total body clearance of MeDDC (volume/time) - DDC diethyldithiocarbamate - f fraction of DDC that is methylated;f=K _DM/K _D - K _A apparent first-order rate constant (reciprocal time) - K _B apparent first-order rate constant (reciprocal time) - K _D apparent first-order rate constant for the elimination of DDC by all routes (reciprocal time) - K _M apparent first-order rate constant for the elimination of MeDDC by all routes (reciprocal time) - K _DE apparent first-order rate constant for the elimination of DDC by all routes except methylation (reciprocal time) - K _DM apparent first-order rate constant for theS-methylation of DDC (reciprocal time) - MeDDC methyl diethyldithiocarbamate - NaDDC sodium diethyldithiocarbamate (trihydrate) - Q zero-order infusion rate constant (mass/time) - Q ₁ zero-order infusion rate constant for the faster of two consecutive infusions (mass/time) - Q ₂ zero-order infusion rate constant for the slower of two consecutive infusions (mass/time) - t elapsed time since dosing (e.g., infusion) commenced - t elapsed time since the cessation of infusion - T duration of infusion (time) - T ₁ duration of the faster of two consecutive infusions (time) - T ₂ total duration of infusion when two consecutive infusions are administered (time) - V _D apparent volume of distribution of DDC - V _M apparent volume of distribution of MeDDC This work was supported by the Atkinson Charitable Foundation (Toronto, Ontario, Canada) and the Non-Medical Use of Drugs Directorate, Health and Welfare Canada (Grant No. 1212-5-206).     

程序升温加速试验计算方法研究

介绍了一种用优选法处理倒数升温和对数升温,用优选法和辛普森积分法处理线性升温加速试验数据的新算法;讨论了常规算法的缺点;比较了3种程序升温方法的优缺点。结果表明,在本文所介绍的新算法中,没有作任何近似处理,克服了常规算法的缺点。在上述3种程序升温方法中,以倒数升温最好,线性升温次之,对数升温较差。     

The effect of nickel chloride on the isolated hemidiaphragm of the rat

• 1.1. NiCl₂ (cumulative concentrations of 0.56–1.91 mmol 1⁻¹) produced concentration-dependent depression of tension developed (Td) and the maximum rate of rise of tension (dT/dt) max) of isometric contraction of the isolated rat hemidiaphragm, during direct subtetanic (DST) electrical stimulation, only. EC₅₀ values for NiCl₂-induced depression of Td and dT/dt max were 0.88 ± 0.06 and 0.83 ± 0.13 mmol 1⁻¹, respectively. NiCl₂ did not significantly change either parameter of the isometric contraction during direct single-pulse (DSP) electrical stimulation.
• 2.2. Maximal depression of Td and dT/dt max, produced by a single concentration of NiCI₂ (1 mmol 1⁻¹) during DST electrical stimulation was obtained 20 min after addition of the drug in the bathing medium.
• 3.3. In the normal Tyrode solution, addition of CaCl₂ (final concentration of 5.86 mmol 1⁻¹) almost completely antagonized the depressant effect of NiCl₂ (1 mmol l⁻¹) on Td and dT/dt max during DST electrical stimulation. In the calcium-free solution, the depression both of Td and dT/dt max produced by NiCl₂ (1 mmol 1⁻¹) was significantly more pronounced in comparison with the effect of NiCl₂ in the normal Tyrode solution.
• 4.4. l-calcium channel activator, Bay K 8644 (25 μmol 1⁻¹), significantly potentiated both Td and dT/dt max during DST electrical stimulation, but NiC1₂ (1 mmol 1⁻¹) decreased both parameters of the isometric contraction even in the presence of this concentration of Bay K 8644. On the other hand Bay K 8644 (25 μmol 1⁻¹) did not antagonize NiCl₂-induced depression of Td and dT/dt max.
• 5.5. Verapamil (2.5 μmol l⁻¹; 45 min of incubation) and lidocaine (0.10 mmol l⁻¹; 30 min of incubation) significantly potentiated the depression of Td and dT/dt max, produced by NiCl₂ (1 mmol l⁻¹), during DST electrical stimulation. The addition of CaCl₂ (final concentration of 7.20 mmol 1⁻¹) in the bathing medium only partially antagonized the depressant synergistic action of both verapamil or lidocaine and NiCl₂ on Td and dT/dt max.
• 6.6. Forskolin (cumulative concentrations of 2.60–44.20 μmol 1⁻¹) fully antagonized NiC1₂-induced depression of both Td and dT/dt max; propranolol (1 μmol l⁻¹) did not abolish this antagonizing action of forskolin. Also, NiCl₂ (cumulative concentrations of 0.56–1.54 mmol 1⁻¹) did not change potentiating effect of forskolin (23.4 μmol 1⁻¹).
• 7.7. In conclusion, NiCl₂-induced depression of both Td and dT/dt max of the isolated rat hemidiaphragm, during DST electrical stimulation could be specific in part, due to the block of calcium influx, and partially non-specific.

     

Pharmacokinetic Analysis of Drug Absorption from Muscle Based on a Physiological Diffusion Model: Effect of Molecular Size on Absorption

In a rabbit hind leg perfusion experiment, the absorption of radiolabeled water and carbohydrates of various molecular sizes from muscle was analyzed using a physiological diffusion model and, also, by statistical moment analysis. The model takes into account diffusion in the interstitial space, transcap-illary movement, and removal by the blood circulation and pharmacokinetic parameters representing these processes were computed by curve-fitting. The apparent diffusion coefficients of water and small sugars in the interstitial space (D _m) were proportional to their free diffusion coefficients in water (D _t), whereas the diffusion of ¹⁴C-inulin was hampered by interstitial structures. The first moments of each absorption process were also determined to assess the quantitative contribution of each absorption process to overall absorption. For carbohydrate molecules, residence time in the depot (t _d) accounted for most of the absorption time after injection, whereas for ³H-water, residence times in muscle (t_m) and in the depot (t_d) were similar.     

Two-compartment dispersion model for analysis of organ perfusion system of drugs by fast inverse laplace transform (FILT)

A dispersion model developed in Chromatographic theory is applied to the analysis of the elution profile in the liver perfusion system of experimental animals. The equation for the dispersion model with the linear nonequilibrium partition between the perfusate and an organ tissue is derived in the Laplace-transformed form, and the fast inverse Laplace transform (FILT) is introduced to the pharmacokinetic field for the manipulation of the transformed equation. By the analysis of the nonlinear least squares method associated with FILT, this model (two-compartment dispersion model) is compared to the model with equilibrium partition between the perfusate and the liver tissue (one-compartment dispersion model) for the outflow curves of ampicillin and oxacillin from the rat liver. The model estimation by Akaike's information criterion (AIC) suggests that the two-compartment dispersion model is more proper than the one-compartment dispersion model to mathematically describe the local disposition of these drugs in the perfusion system. The blood space in the liver, V_B, and the dispersion number D_N are estimated at 1.30 ml (±0.23 SD) and 0.051 (±0.023 SD), respectively, both of which are independent of the drugs. The efficiency number, R_N, of ampicillin is 0.044 (±0.049 SD) which is significantly smaller than 0.704 (±0.101 SD) of oxacillin. The parameters in the two-compartment dispersion model are correlated to the recovery ratio, F_H, mean transit time, ¯t_H, and the relative variance, ²/¯t_H ², of the elution profile of drugs from the rat liver.Notation A Cross-sectional area of the blood space - C(t, z) Concentration of drug (one-compartment dispersion model) - C(s, z) Laplace transform of C(t, z) - C ₁(t, z) Concentration of drug in blood space (two-compartment dispersion model) - C ₂(t, z) Concentration of drug in the liver tissue (two-compartment dispersion model) - C ₁ (s, z) Laplace transform ofC ₁(t, z) - D Axial or longitudinal dispersion coefficient - D _c(=D· A ²) Corrected dispersion coefficient - D _N Dispersion number - f _I(t) Input function with respect tot - f_I(z) Input function with respect toz - F_I(s) Laplace transform of f_I(t) - f_s(t) System weight function with respect tot - f_s(z) System weight function with respect to z - F_H Recovery ratio - k Partition ratio (distribution ratio) - k₁₂, k₂₁ Forward and backward partition rate constant in the central elimination two-compartment dispersion model - k ₁₂ ^p ,k ₂₁ ^p Forward and backward partition rate constant in the peripheral elimination two-compartment dispersion model - k_e Elimination (or irreversible transfer) rate constant - k _e ^p Elimination rate constant in peripheral elimination model - K_H Distribution constant - L Length of blood space in liver - M Amount of drug injected - m Coefficient related to the injected amount - p_h Mass transfer coefficient from perfusate to hepatic tissue - Q Flow rate of perfusate - R_N Efficiency number - s Laplace variable - t Time - ¯ t_H Mean transit time - Linear flow velocity of the perfusate - V _B(= L·A) Blood volume (sum of the sinusoid volume and the space of Disse) - v_h Apparent volume of distribution - V _H Anatomical volume of liver tissue - z Axial coordinate in the liver - (t) Delta function - Volume ratio of the anatomical liver tissue to the blood space - ² Variance of transit time - ²/¯t _H ² Relative dispersion to transit time - Partial derivatives     

The effect of streptozotocin‐induced diabetes on cardiac β‐adrenoceptor subtypes in the rat

1 The present study investigates the effect of short‐term experimental diabetes of 14‐days duration on the β‐adrenoceptor subtypes of the rat heart. 2 β‐adrenoceptor‐mediated functional responses to submaximal doses of isoprenaline were enhanced in Langendorff‐perfused hearts from diabetic rats, manifested as greater changes in tension, heart rate and rates of tension development (+dT/dt) and decline (–dT/dt). 3 Radioligand binding data demonstrated that total cardiac β‐adrenoceptor density and affinity for [³H]‐dihydroalprenolol was unchanged by diabetes, although a decrease in β₁‐adrenoceptor density and increase in β₂‐adrenoceptor density was observed. 4 In conclusion, hearts from 14‐day streptozotocin‐induced diabetic rats demonstrate a number of alterations within the β‐adrenoceptor system. However, the enhanced β‐adrenoceptor‐mediated responses to isoprenaline were not caused by an overall increase in density of β‐adrenoceptors, but were accompanied by changes in the ratio of the β‐adrenoceptor subtypes.     

Influence of uridine diphosphate (UDP)-glucuronosyltransferases and ABCC2 genetic polymorphisms on the pharmacokinetics of mycophenolic acid and its metabolites in Chinese renal transplant recipients

The aim was to investigate the effect of UGT1A9, UGT1A8, UGT2B7 and ABCC2 polymorphism on the pharmacokinetics of mycophenolic acid (MPA) and its metabolites phenolic glucuronide (MPAG) and acyl glucuronide (AcMPAG) in Chinese renal transplant recipients. Single nucleotide polymorphisms (SNP) in UGT1A9-118(dT)₉/₁₀, UGT1A9 T-440C/C-331T, UGT1A8*3, UGT2B7 G211T, UGT2B7 C802T, ABCC2 C-24T, and ABCC2 G1249A were detected. A total of 46 recipients were enrolled in the pharmacokinetics study at day 30 after kidney transplantation. Differences in the MPA pharmacokinetic profiles confirmed large inter-patient variation of MPA exposure. A statistical significant increase in the dose-adjusted AUC_6–12 level of MPA was found in patients bearing the -118(dT)₁₀ allele of the UGT1A9 gene (T₉ = 7.34 ± 4.11 mg h ml^?1 g^?1; T₉/T₁₀ = 11.54 ± 7.62 mg h ml^?1 g^?1; and T₁₀ = 11.89 ±8.76 mg h ml^?1 g^?1, p = 0.041). A similar trend was also observed for the dose-adjusted AUC_0–12 and AUC_6–12 of MPAG. Patients carrying the heterozygous mutant alleles of ABCC2 G1249A exhibited higher AUC_6–12/D of AcMPAG than those with wild-type genotype (p = 0.016). The other SNPs that were genotyped did not cause any significant variation in MPA and MPAG pharmacokinetic parameters. In conclusion, the enterohepatic recirculation of MPA in the patients seems to be more extensive in UGT1A9-118(dT)₁₀ allele carriers, and the exposure of AcMPAG is higher in patients carrying ABCC2 G1249A genotype than those with wild-type genotype.     

Computer-controlled heating system and new computation for reciprocal heating stability experiment

A computer-controlled heating system and a new computation with optimization for reciprocal heating experiment have been introduced. In the heating system, a pocket computer was used to control a common thermostat to obtain different heating models. This system is simple, reliable and inexpensive. Its temperature range is 0–97°C for the water bath or 0–200°C for the oven. The accuracy and precision of temperature are ≤ 0.5°C in the range 0–100°C or ≤ 1% in the range 100–200°C; the resolution is 0.05°C; the fluctuation is 0.05°C for the water bath or ≤ 0.5°C for the oven; and time is accurate to ≤ 5 s per month. A comparison of the new and conventional computations is discussed. The results indicate that the deficiencies of the conventional computation have been overcome.     

栀子-闹羊花配伍对大鼠血浆中闹羊花毒素Ⅱ和闹羊花毒素Ⅲ的药动学影响

目的考察栀子与闹羊花配伍对闹羊花中闹羊花毒素Ⅱ和闹羊花毒素Ⅲ药动学的影响。方法建立LC-MS/MS测定大鼠血浆中闹羊花毒素Ⅱ和闹羊花毒素Ⅲ的分析方法,并用此方法测定大鼠口服给予闹羊花与栀子配伍液及闹羊花单煎液后大鼠体内的闹羊花毒素Ⅱ和闹羊花毒素Ⅲ的血药浓度,计算其药动学参数并统计分析。结果闹羊花毒素Ⅱ在1～200 ng·mL^–1、闹羊花毒素Ⅲ在1～100 ng·mL^–1内线性关系良好(r>0.999),质控样本精密度均<12%,准确度RSD<20%。栀子配伍闹羊花给药和单独给药后体内闹羊花毒素Ⅱ的AUC_0–t分别为(260.44±51.67)和(213.39±59.03) h·ng·mL^–1,闹羊花毒素Ⅲ的AUC_0–t分别为(60.97±22.78)和(22.38±5.55)h·ng·mL^–1。与闹羊花单煎给药相比,栀子与闹羊花配伍给药后闹羊花毒素Ⅱ的T_1/2和MRT₍(0–t))显著升高,闹羊...