小■碱敏感场效应传感器的研制

Berberine-tetraphenylborate was studied as an electrically active material for electrode membrane. The membrane was coated on a platinum-wire connected with MOSFET paling electrode to make a berberine-ISFET. The berberine-ISFET showed Nernstian response in 10^-2～10^-6 mol/L berberine solution over pH 3.5～11.0 with a slope of 57±1 mV/decade.     

异戊巴比妥选择电极的研制及初步应用

An amobarbital-selective electrode based on amobarbital-triheptyldodecylammonium ionpairs in nitrobenzene was prepared and studied. The electrode showed a linear response to amobarbital anion within 2 × 10^-2～5 × 10^-5M concentration range in 0.1M Na₂CO₃ medium. The slope of the electrode was 57 mV/ decade and the limit of detection was 2 × 10^-5M. The electrode can be used for the determination, of amobarbital in drug-substances by direct potentiometry or potentiometric titration with standard solution of sulfuric acid. Dissociation of electroactive material in liquid ion exchanger is also discussed in the paper.     

扑尔敏—PVC膜电极的制备及其应用

An ion selective electrode for chlorpheniramine (CP) was studied. The PVC(polyvinyl chloride)matrix membrane was prepared by the CP-tetraphenylborate salt, dibutyl phthalate and 10% PVC-tetrahydrofuran solution in weight ratio of 0.007:0.69:3.0. The CP ion electrode shows Nernstian range from 1×10-2 to 1×10^-5M in the pH range of 5～7, with an average slope of 56.0±0.1 mV/decade. Paracetamol (4-acetamidophenol), aminopyrine, caffeine, moroxydine, sodium benzoate etc do not interfere, whereas phenergan (promethazine) ion interferes. The electrode is useful as an indicator for the precipitation titration of CP and some of its preparations with sodium tetraphenylborate.     

甲基黄酮醇胺盐酸盐对β受体的阻断作用

The β-receptor blocking action of methylflavonolamine hydrochloride(MFA) was studied and compared with those of propranolol. The doseresponse curves of isoproterenol were shifted to the right by MFA on isolated rabbit atrium in this experiment. The pA₂ value and the slope of the regression line of MFA calculated from Schild plot were 5.53 and -0.84 respectively. The effects of MFA and propranolol on duck erythrocyte membranes were studied by the radioligand binding method. Both MFA and propranolol inhibited the binding of [³H] dihydroalprenolol to β-receptors. Their apparent equilibrium dissociation constants were 1.12×10^-5 mol/L and 5.50×10^-9 mol/L respectively. The affinity of propranolol to β-receptors of duck erythrocyte membranes was 2039-fold higher than that of MFA. These results demonstrates that MFA is a weak competitive β-receptor blocking agent.     

一叶萩碱对5种神经递质受体和蛙脊髓膜电位的影响

Using radioligand binding assay method, securinine was shown to be specifically bound to GABA receptors of rat brain with IC₅₀ of 10^(-4)～10^-5mol/L. However, securinine did not exhibit affinity for a₁-, a₂- adrenoceptors and M-cholinergic receptors of rat brain and the β-adrenoceptors of duck erythrocyte membrane. In isolated and perfused bullfrog spinal cord experiment, the depolarization induced by GABA was slightly depressed by securinine (1 mmol/L), but no antagonistic effect on glycine or taurine evoked depolarization was observed with securinine. These results indicate that securinine is a weak GABA antagonist.     

Monocyte and neutrophil direct counts correlate with C-reactive protein plasma concentration in patients with acute pancreatitis

Acute pancreatitis (AP) is associated with the intensive inflammatory response in white blood cells (WBC) and C-reactive protein (CRP). This paper presents the relationship between the CRP plasma concentration and the direct counts of peripheral WBC in AP during the initial five days. The study consisted of 56 patients with AP, 36 patients with mild form of AP and 20 patients with severe form of AP. ABX VegaRetic hematological analyzer was used to perform the count of blood cells, and the immunonephelometric method was performed to measure the CRP concentration levels. AP patients presented with WBC count values in the range of 3.2 − 22.4 × 10³/μl and CRP concentration levels in the range 3.3 − 599.8 mg/l. The WBC count correlates with CRP levels during the entire observation period. The relationship of CRP and WBC is expressed in the following regression equation: WBC (10³/μl) = 3.66 + 1.40 × log_eCRP (mg/l). The highest median neutrophil count (8.15 × 10³/μl) was observed on the first day. The count decreased to 5.27 × 10³/μl on the fifth day. The most substantial finding in this study involved the values found for the monocytes and CRP (r= 0.53; p<0.001). Day two and day three were the highest (r=0.59, p<0.001). On day two, the regression equation for this relationship is: Monocytes (10³/μl) = −0.34 + 0.21 × log_eCRP(mg/l). The correlation between direct monocyte count and plasma CRP concentration in AP reflect a CRP-dependent stimulation of IL-6 release from activated blood monocytes.     

Δ16-娠烯-3β-乙酰氧基-11:20-二酮的极谱测定

A simple and rapid method for the determination of △~(16)—pregnene-3β—acetoxy — 11:20 — dione has been worked out. In an aqueous 40% iso-propanol solution of 0.1N NH₄Cl, this steroid gave a double polarographic wave which could be used for its determination. The current was measured at —1.50 v. vs. S.C.E. and was proportional to the concentration in the range of 36 to 180/μg/ml. From the experimental results, the diffusion current constant I and the diffusion coefficient D have been calculated to be 1.30 and 1.15 ×10^-6 cm²/sec. respectively. This method has been applied to the analysis of a sample; the result agreed with that obtained by the spectrophotometric method.     

β肾上腺素受体不可逆阻断剂BAlpM的合成

A highly potent beta-adrenergic irreversible antagonist——Bromoacetylalprenololmenthane (BAlpM)was synthesized by a Six step method with phenol and allychloride as the starting materials. Some improvement on purification of the product was described. The final product is identified by melting point, elemental analysis, UV and IR spectral analysis and mass spetrometry as well as β-adrenergic receptor bindingassays. [¹²⁵I]±IODOPINDOLOL binding assay of mouse lung cell membrane preparations treated with BAlpM in vitro or in vivo showed that there was a dosedependant decrease in the density of specific binding sites with no change in the Kd values. This result confirms that BAlpM is a β-adrenergic irreversible antagonist.     

LC-MS/MS法测定人血浆中西酞普兰及其在制剂生物等效性中的应用

A sensitive and selective LC-MS/MS method for determination of citalopram in human plasma was established to study the bioequivalence of different formulations containing citalopram. The samples were simply pretreated by protein precipitation using acetonitrile, and then analyzed on a Zorbax Extend C₈column. The mobile phase consisted of acetonitrile-water-formic acid (60∶40∶0.2), at a flow-rate of 0.5 mL·min^-1. A Thermo Finnigan TSQ Quantum Ultra tandem mass spectrometer equipped with electrospray ionization source was used as detector and was operated in the positive ion mode. Selected reaction monitoring using the precursor to product ion combinations of m/z325 → m/z109 and m/z265 → m/z167 was performed to quantify citalopram and the internal standard, respectively. The pharmacokinetic parameters of citalopram in different formulations were calculated by non-compartment model. The linear calibration curves were obtained in the concentration range of 0.10-100 μg·L^-1. The lower limit of quantification was 0.10 μg·L^-1. The intra- and inter-day relative standard deviation (RSD) over the entire concentration range was less than 5.2%. Accuracy determined at three concentrations (0.25, 8.00 and 90.0 μg·L^-1 for citalopram) ranged from -4.7% to 1.3%. Each plasma sample was chromatographed within 3.0 min. The method was successfully used in bioequivalence study of citalopram in human plasma after oral administration of 20 mg citalopram. Calculated with AUC_{1-120 h}, the bioavailability of two formulations was (102.1±10.9)%. The method is rapid, selective, robust and is proved to be suitable for bioequivalence evaluation of different formulations containing citalopram.     

Heterogeneous characteristics of imidazoline-induced insulin secretion

Imidazolines are regarded as a pharmacological group of insulin secretagogues with one uniform mechanism of action, namely closure of ATP-dependent K⁺ channels (K_ATP channels) and, in consequence, depolarization of the plasma membrane, Ca²⁺ influx and stimulation of secretion. This assumption was investigated by measuring insulin secretion from perifused pancreatic islets in response to three imidazoline compounds and comparing the characteristics of secretion with changes in membrane potential and cytosolic Ca²⁺ concentration [Ca²⁺]_i of single β-cells. Phentolamine (32 μM) stimulated insulin secretion from perifused mouse islets in the presence of stimulatory (10 mM and 30 mM) and substimulatory (5 mM) glucose concentrations and even in the absence of glucose. Idazoxan in concentrations up to 500 μM was virtually ineffective in the presence of 5 mM glucose. At 10 mM glucose, there was a moderate but significant increase of secretion by idazoxan, 20 μM being nearly as effective as 100 μM. The effect of phentolamine was of slow onset and irreversible in the time frame of the experiments, while the effect of idazoxan was of fast onset and reversible. Alinidine also stimulated secretion in the presence of 10 mM glucose with fast and reversible kinetics, but in contrast to idazoxan, 100 μM was clearly more effective than 20 μM. These heterogeneous characteristics of secretion were reflected by changes of [Ca²⁺]_i: the increase of [Ca²⁺]_i by phentolamine was slow and only partially reversible, whereas idazoxan led to a smaller, but faster and reversible response. The increase of [Ca²⁺]_i by phentolamine and idazoxan was abolished by the Ca²⁺ channel blocker D 600. Surprisingly, all three compounds depolarized the β-cell plasma membrane from a resting potential of –71 mV to about –36 mV. Again, the effect of phentolamine was slow and that of idazoxan and alinidine fast. Thus, the characteristics of phentolamine-induced secretion appear to be attributable to the consequences of K_ATP channel closure. It is unclear, however, why all three test compounds achieved the same degree of depolarization in spite of their known different efficiency to close K_ATP channels. Apparently, there are additional mechanisms involved in the action of idazoxan and alinidine, which may contribute to the obvious differences in the characteristics of secretion. Received: 2 October 1998 / Accepted: 21 December 1998     

甲氧苄氨嘧啶(TMP)的电分析化学研究及其在药物分析中的应用

本文用微分脉冲极谱法和循环伏安法研究了甲氧苄氨嘧啶(TMP)的电化学行为,选择了最佳的测定条件,TMP的检出限可达2.0×10^-7mol/L,方法灵敏度较高,并研制了TMP-PVC膜离子选择性电极,试验了该电极的各种特性及Nernst响应范围。本法应用于制剂中TMP的测定,选择性好,干扰少,毋须分离,方法简便快速。选择电极在人尿和血清的介质中测定,也能获得良好的结果。     

变价态唐松草新碱—PVC膜离子选择电极的研制及解离常数的测定

本文研制了以四苯硼—唐松草新碱缔合物为电活性物质的变价态唐松草新碱—PVC膜电极。电极膜按电活性物质:PVC:DBP为1:8:8组成。该电极在pH 5.0～6.0,Ⅰ=0.05的NaCl—HCl溶液中Nernst响应范围为1×10^-3～1×10^-5mol/L。电极斜率为58.2 mV/logc。检测限为2.5×10^-6mol/L。用直接电位法考察了TDH⁺,TDH₂CF⁺⁺共存时溶液pH和电极斜率S的关系。用S—pH关系,测定了25℃,Ⅰ=0.05时的Ka₁值为(2.5±0.2)×10^-4,用E—pH关系,测定了25℃,Ⅰ=0.05时的Ka₂值为(8.1±0.9)×10^-8。     

ClO4-场效应敏感器件的研制及其在药物分析中的应用

应用碱性染料和乙基紫与ClO_4~-离子形成缔合物作为活性材料研制的PVC膜ClO_4~-电极,国内已有报道,本器件离子敏感膜是以十六烷基吡啶与ClO_4~-离子形成离子缔合物为活性材料,研制成涂丝ClO_4~-场效应敏感器件(ClO~4~-—ion sensitive field effect transistor简称为ClO_4~--ISFET);测定了器件的各项性能参数,并用于测定了药物溴化丙胺太林、苯扎溴铵,获得了较为满意的结果。     

利多卡因电极的制备及其分析性能研究

本文报道以四间氯苯硼酸为载体的利多卡因选择性电极,研究了增塑剂对电极性能的影响,确定了邻苯二甲酸二壬酯为该电极最佳的溶剂介质。电极的线性范围为6.3×10^-6～1.0×10^-1mol/L,斜率59.5 mV/pC(25℃),检测下限为1.1×10^-5mol/L,电极适用的pH范围为2.7～6.1,讨论了各种药物的电位选择性系数和分子连接性指数之间的相关性。     

尼群地平几种测定方法的比较

本文研究并比较了三种测定抗心血管病药尼群地平的方法:氰离子选择电极法、示波极谱法和紫外分光光度法。氰离子选择电极法在10^-3～5×10^-6mol/L范围有Nernst响应,示波极谱法的线性范围为10^-3～10^-6mol/L,紫外分光光度法线性范围为10^-4～10^-6mol/L。三种方法均有相当的重现性和精密度,可用于原料药及片剂中尼群地平含量的测定。     

服止宁离子选择电极的研制

以四苯硼钠和服止宁形成的离子缔合物为活性物质研制了服止宁液膜和PVC膜电极。液膜电极的响应范围为10^-2～5×10~(-5)M,PVC膜电极的响应范围为10^-2～10^-5M。PVC膜电极的响应斜率比液膜电极的高,且响应迅速、重现和稳定。用分别溶液法测了电极对24种物质的选择性系数,结果表明少数叔胺类、季铵类生物碱有干扰。用这种电极测定了服止宁原粉及其片剂的含量,原粉的平均回收率为99.7%,标准偏差为±1.8%,片剂的标准偏差为±0.43%。     

可卡因膜电极的研制及应用

研制了以二苦胺可卡因、四硫氰基二氨铬酸可卡因、四苯硼酸可卡因离子缔合物为活性物质的可卡因膜电极并比较了它们的响应特性。三种电极的检出限度约为10^-5mol/L。其中以可卡因—二苦胺膜电极响应特性最好。这一电极在5×10^-2～2×10^-5mol/L范围内线性响应良好,平均斜率为59.3mV/log C,响应迅速,重现性良好;由电位滴定法测定盐酸可卡因和由直接电位法测定盐酸可卡因溶液,得到了满意的结果。     

涂碳式聚氯乙烯膜双嘧达莫选择电极的研制与应用

目的建立用涂碳式聚氯乙烯膜双嘧达莫电极测定双嘧达莫片含量的方法。方法利用该电极对双嘧达莫的响应 ,测定双嘧达莫片含量。结果平均回收率为 98 6 % ,RSD≤ 4 37% ,响应范围为 4 2× 10 -3 ～ 3 0× 10 -5mol·L-1,检测限为 1 7× 10 -5mol·L-1。结论涂碳式聚氯乙烯膜电极法可简便、快速、准确地检测片剂中双嘧达莫的含量。     

匹鲁卡品的电分析化学研究

本文用微分脉冲极谱法和循环伏安法研究了匹鲁卡品的电化学行为,选择了Zn(Ⅱ)—匹鲁卡品法测定的最佳条件,建立了测定方法,俭出限可达8.0×10^-7mol/L;同时还制备了匹鲁卡品—PVC膜离子选择性电极,直接应用于匹鲁卡品注射液的测定,毋需分离,简便快速,结果良好。