含硫药物的氧瓶燃烧—电位滴定法测定

建立了一种测定含硫药物的方法。利用氧瓶燃烧法使分子中的硫元素转化为SO₄^2-,然后通过蒸发,加维生素C分解过氧化氢以及加入无水乙醇和1.4—二氧六环等步骤,再用硝酸铅标准溶液以铅离子选择性电极作指示电极进行电位滴定,籍此测定含硫药物的含量。用此法测定了一组含硫药物原料药和几种制剂,经与药典法比较,结果一致。方法简便,在混合物分析中有一定的选择性。     

血清钾、钠离子选择性电极间接法与酶法测定的相关性分析

目的:对钾、钠离子选择性电极间接法测定与酶法测定的相关性进行比较,以确定离子选择性电极间接法与酶法的相关性。方法:通过对50例正常体检人群的血清钾、钠离子分别用离子选择性电极间接法和酶法同时分别测定。结果:离子选择性电极间接法和酶法相比,离子选择性电极间接法比酶法结果略高,但二者具有良好的相关性,与文献相符。结论:离子选择性电极间接法与酶法结果具有良好的相关性(P0.05)。离子选择性电极间接法测定标准差比酶法标准差低,具有更好的精密度。     

维生素B1注射液的氯离子选择性电极电位滴定法测定

以氯离子选择性电极为指示电极，甘汞电极为参比电极，用电位滴定法测定维生素B1注射液的含量，通过电位突跃来判断滴定终点。本法的测定结果与药典法基本一致。     

洛美沙星选择性电极的制备及应用

目的：制备一种以洛美沙星与四苯硼钠缔合物为活性物的PVC膜洛美沙星选择性电极。方法：用此电极以标准曲线法对盐酸洛美沙星及二种制剂进行含量测定。结果：电极的响应范围10^-1-10-5mol/L，斜率为51.4mV/pC，测得平均回收率为98.1%,RSD=2.6%(n=8)。结论：方法灵敏度高，操作简便，结果与HPLC法相符。     

环丙沙星离子选择性电极的制备及应用

目的：制备一种以环丙沙星与四苯硼钠缔合物为活性物的PVC膜环丙沙星选择性电极。方法：用此电极以标准曲线法对盐酸环丙沙星及其两种制剂进行含量测定。结果：电极的响应范围10^-1～10^-5mol·L^-1，斜率为37．4mv／pC，平均回收率为97．7％，RSD=2．4％（n=8）。结论：方法灵敏度高，操作简便，结果与HPLC法相符。     

生物电极与药物研究

生物电极是八十年代由酶电极发展起来的新技术,它是分析工作者的有用探针。本文仅就生物电极及其在药物研究上的应用作一概要介绍。酶电极及其原理酶电极是一种敏化离子选择性电极。是由一种高度专属性、高度敏感的催化试剂的酶和一种离子选择性电极所构成。这种电极最适用于测定酶的底物、辅酶和抑制剂,故称为酶电     

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。     

氧瓶燃烧法-氟离子选择电极法测定司氟沙星片的含氟量

目的:用氟离子选择性电极测定经氧瓶燃烧破坏后的司氟沙星含量,建立一种利用氟离子选择性电极进行定量分析的新方法。方法:药物经氧瓶燃烧有机破坏,使氟离子游离于吸收液中,对吸收液进行适当处理后用氟离子选择电极测其电位值,根据标准曲线测定含量。结果:司氟沙星片中氟离子浓度在2.0×10~(-6)～2.0×10~(-2)mg·ml~(-1)范围标准曲线线性良好,r=0.999 8,方法回收率为99.48%。结论:该方法简单准确,可以用来进行司氟沙星的含量测定。     

药物离子选择性电极的研究与进展

药物离子选择性电极(以下简称药物电极)是借助离子选择性电极的原理研制的对某一特定药物有较好选择性的电化学传感元件。由于药物电极分析方法有一系列优点,如;电极制作容易、操作简便、不需大型贵重仪器、测量快速、线性响应范围一般较宽、许多无机离子与低分子量有机物无显著干扰、可用于有色或混浊溶液、可制成微型电极用以测定微量样     

测定某些有机药物的通用石墨内导PVC膜电极

用石墨作内部接触制备了一种通用PVC膜电极,可用于某些药物的分析测定。PVC膜用十六烷基三辛基碘化铵作定域体,并用邻苯二甲酸二丁酯作溶剂介体,测定某一药物时,用相应药物的溶液活化电极。报道了电极对苯巴比妥,硫喷妥,异戊巴比妥、苯妥英、利尿酸及水杨酸的电位响应特性及最佳pH与浓度区间。用该电极测定上述药物获得了较好的回收率。     

Metabolism of 3-tert-butyl-4-hydroxyanisole by horseradish peroxidase and hydrogen peroxide.

3-Tert-butyl-4-hydroxyanisole (3-BHA) was metabolized in the presence of horseradish peroxidase and hydrogen peroxide to 2-tert-butyl-p-benzoquinone (TBQ), 2,3-epoxy-5-tert-butyl-1,4-benzoquinone (TBQ-epoxide), and two known dimers. The formation of TBQ from 3-BHA required both horseradish peroxidase and hydrogen peroxide. When 2.5 mM 3-BHA was incubated with horseradish peroxidase and hydrogen peroxide, the formation of TBQ increased with hydrogen peroxide concentration up to 5 mM and decreased gradually at higher concentrations of hydrogen peroxide. On the other hand, the formation of TBQ-epoxide from 3-BHA increased, depending on hydrogen peroxide concentration at higher concentrations than 1 mM. In incubating 2-tert-butylhydroquinone (TBHQ) with horseradish peroxidase and hydrogen peroxide, TBHQ was rapidly oxidized to TBQ, and then TBQ-epoxide was also produced at concentrations more than 2.5 mM of hydrogen peroxide. In the absence of horseradish peroxidase, the incubation of TBQ with hydrogen peroxide resulted in TBQ-epoxide production. These results suggest that 3-BHA is metabolized to TBHQ, which is rapidly oxidized to TBQ, by horseradish peroxidase and hydrogen peroxide, and then TBQ is converted to TBQ-epoxide by only hydrogen peroxide.     

Metabolic N-oxidation of metronidazole

Metronidazole when treated at the N-3 nitrogen with a mixture of hydrogen peroxide and acetic acid, or liver homogenate preparations, yields the N-3 oxide as identified by thin-layer chromatographic analysis on silica gel G, RF 0.62 in ethanol-chloroform-ammonia (50:49:1), by chemical reduction with sulphur dioxide, and by ultra-violet spectrophotometry and nuclear magnetic resonance spectroscopy. Incubation of metronidazole at 37 degrees C with rat liver 10,000g supernatant fortified with cofactors gave a product with identical chromatographic and UV spectral data suggesting that metronidazole like other tertiary amine drugs undergoes microsomal N-oxidation.     

Transformation of 2,2'-anhydro-1-beta-D-arabinofuranosylcytosine induced by hydrogen peroxide.

2,2'-Anhydro-1-beta-D-arabinofuranosylcytosine (I) is a more potent and less toxic antineoplastic agent than is cytarabine (1-beta-D-arabinofuranosylcytosine) (II). The anhydronucleoside (I) was found to be readily transformed by hydrogen peroxide into 2,2'-anhydro-5-hydroxy-1-beta-D-arabinofuranosylcytosine (III) by treatment with 0.025 M hydrogen peroxide at a neutral and slightly basic pH range (pH 6-9) and at room temperature. It was converted into non-UV-absorbing substance(s) by hydrogen peroxide at an alkaline pH (pH 11). Since hydrogen peroxide is produced by redox reactions in all living cells, it may be responsible for the alteration of I. Such transformations by hydrogen peroxide were not observed with cytarabine.     

过氧化氢酶间接碘量法测定吐温80中过氧化氢的含量

目的:用过氧化氢酶间接碘量法测定吐温80中非法加入的过氧化氢的含量。方法:用过氧化氢酶分解样品中的过氧化氢,通过间接碘量法测定分解前后样品中强氧化物的含量,计算样品中过氧化氢的含量。结果:检测了7个厂家18批吐温80中过氧化氢的含量,所有样品全都检测出含有过氧化氢,最高达到了185.3μg·g-1。结论:作为注射剂常用的药用辅料,吐温80中残留的过氧化氢会对注射剂的安全造成严重影响,利用本法可以简便、快捷的检测出过氧化氢含量。     

Effect of hydrogen peroxide on the initiation of microsomal lipid peroxidation

Hydrogen peroxide reacts with reduced transition metals to generate the highly reactive hydroxyl radical (·OH), most often proposed as the predominant species for initiating microsomal lipid peroxidation. To assess the potential involvement of ·OH, generated from hydrogen peroxide, in microsomal lipid peroxidation, we have altered the concentration of microsomal hydrogen peroxide and measured the resulting rates of malondialdehyde production. Hydrogen peroxide concentration in microsomes was changed by adding exogenous catalase, by washing to reduce both endogenous catalase activity and hydrogen peroxide-dependent glutathione oxidase activity, and by inhibiting endogenous catalase activity with azide in either the presence or absence of exogenous hydrogen peroxide. In only one instance was the rate of lipid peroxidation affected; exogenous hydrogen peroxide added to microsomes, previously incubated with azide, inhibited lipid peroxidation, the opposite effect from that predicted if ·OH, generated from hydrogen peroxide, is actually the major initiating species. Neither these results, nor the inability of known ·OH traps to inhibit microsomal lipid peroxidation, support the role of free hydrogen peroxide in the initiation of microsomal lipid peroxidation.     

Drug-induced hydrogen peroxide production in isolated rat hepatocytes

A method for measuring drug-induced hydrogen peroxide production in freshly isolated rat hepatocytes is described. 3-Amino-1,2,4-triazole, an irreversible inhibitor of the enzyme catalase markedly reduces the capacity of isolated hepatocytes to metabolize hydrogen peroxide, with maximum inhibition (80%) being observed after 40 min of co-incubation. The present method is based on the observation that this inhibition of catalase by 3-amino-1,2,4-triazole is prevented by methanol and that the effect of methanol is reversed in the presence of hydrogen peroxide. Using this assay we could demonstrate increased hydrogen peroxide production during the metabolism of diquat, paraquat, xanthine, benzylamine and glycolate by hepatocytes. Inhibition of the hydrogen peroxide metabolic capacity was greatest with glycolate and diquat, whereas paraquat and benzylamine only had a minor effect.     

Mechanism of resistance to oxidative stress in doxorubicin resistant cells

Doxorubicin (DOX) is an anthracycline drug widely used in chemotherapy for cancer patients, but it often gives rise to multidrug resistance in cancer cells. The purpose of this work was to study the effect of hydrogen peroxide in DOX-sensitive mouse P388/S leukemia cells and in the DOX-resistant cell line. Hydrogen peroxide induced a significant increase in dose- and time-response cell death in cultured P388/S cells. The degree of cell death in P388/DOX cells induced by hydrogen peroxide was less than that in P388/S cells treated with hydrogen peroxide. Parent cells exposed to 3 mM of hydrogen peroxide showed a loss of mitochondrial membrane potential correlated with cell death. Hydrogen peroxide at a concentration greater than 0.3 mM increased the intracellular Ca2+ of P388/S cells dose-dependently; however, no change following addition of hydrogen peroxide (0.3-1 mM) was observed in the resistant cells. Hydrogen peroxide (0.1 and 1 mM) treatment also induced the production of intracellular ROS in P388/S cells, while no such increase was produced by this substance in P388/DOX cells. Resistant cells also showed a significant level of glutathione (GSH) compared with the parent cells. In addition, N-acetyl-L-cysteine and reduced GSH antioxidants abolished death of P388/S cells caused by hydrogen peroxide. Therefore, it is believed that the reduced effect of oxidative stress towards the resistant cells may be related to an increase in intracellular GSH level.     

Significance of endogenous sulphur‐containing gases in the cardiovascular system

1. The sulphur‐containing gases hydrogen sulphide and sulphur dioxide can be generated endogenously in mammalian tissues and exert significant biological effects in the cardiovascular system. Hydrogen sulphide is considered to be the third novel gasotransmitter in addition to nitric oxide and carbon monoxide. The present review describes the effects of hydrogen sulphide on the cardiovascular system and its possible mechanisms under physiological conditions. We also discuss the pathophysiological effects of hydrogen sulphide on cardiovascular diseases. The therapeutic potential of hydrogen sulphide is summarized. 2. We recently discovered that sulphur dioxide, another endogenous sulphur‐containing gas, has important physiological and pathophysiological roles in the cardiovascular system. To some extent, the effect of sulphur dioxide is similar to that of the other gasotransmitters nitric oxide, carbon monoxide and hydrogen sulphide. Sulphur dioxide may also be a novel gas mediator in the cardiovascular system.     

Mechanisms of hydrogen peroxide-induced relaxation in rabbit mesenteric small artery

The effects of hydrogen peroxide were studied on isolated rabbit mesenteric small artery; rabbit superior mesenteric artery and mouse aorta were also studied as reference tissues. For mesenteric small artery, hydrogen peroxide (1 to 100 microM) relaxed a norepinephrine-stimulated artery in a concentration-dependent manner. The relaxation was not significantly affected by removal of the endothelium and was less pronounced in arteries contracted with high-KCl solution plus norepinephrine than in those contracted with norepinephrine alone. The relaxation response to hydrogen peroxide was increased by isobutylmethylxanthine and zaprinast, inhibited by diclofenac, methylene blue and dithiothreitol and unaffected by atropine, tetraethylammonium, superoxide dismutase, deferoxamine, dimethyl sulfoxide or the Rp stereoisomer of adenosine cyclic monophosphothioate. Hydrogen peroxide shifted concentration-contractile response curves for norepinephrine to the right and downwards. Norepinephrine and caffeine elicited a transient, phasic contraction of the mesenteric small artery exposed for 0.5, 1 and 2 min to a Ca2+-free solution. Hydrogen peroxide inhibited the norepinephrine-induced contraction, and to a lesser extent the caffeine-induced contraction, and verapamil did not alter the contraction to norepinephrine. These pharmacological properties of hydrogen peroxide were similar to those of 8-bromo cGMP; 8-bromo cGMP inhibited more potently the norepinephrine-induced than the KCl-induced contraction and the contraction elicited by norepinephrine in Ca2+-free solution. The present results suggest that hydrogen peroxide induces endothelium-independent relaxation of the rabbit mesenteric small artery precontracted with norepinephrine. The effects of hydrogen peroxide may be at least in part mediated by cGMP and cyclooxygenase products in the vascular smooth muscles now used.     

Mechanism of inactivation of myeloperoxidase by propylthiouracil

The mechanism of inactivation of myeloperoxidase purified from rat bone marrow by propylthiouracil (PTU) was studied. PTU inhibited not only the peroxidase activity but also the chlorinating activity of myeloperoxidase in a concentration dependent manner. When myeloperoxidase was treated with PTU and hydrogen peroxide (5 microM), inactivation of the enzyme was still observed after the excess reagents were removed by a column of Sephadex G-25. The treatment of the enzyme with PTU in the absence of hydrogen peroxide caused a slight inhibition of the enzyme activity. In addition, [14C]PTU became bound to myeloperoxidase in the presence of hydrogen peroxide. Difference spectrum of myeloperoxidase incubated with the small (0.1 mM) and large (2 mM) amounts of hydrogen peroxide revealed the formation of compounds II and III, respectively. Difference spectrum of myeloperoxidase treated with PTU in the presence of a low concentration of hydrogen peroxide (5 microM) was similar to that of compound II. Therefore, these results indicate that PTU inactivates myeloperoxidase through binding to the enzyme and the conversion to a compound II-like form in the presence of hydrogen peroxide.