Determination of analytical error function for β-blockers as a possible weighting method for the estimation of the regression parameters

Three analytical methods have been developed and validated for the quantification of β-blockers (celiprolol, bisoprolol and oxprenolol) using high performance liquid chromatography (HPLC) with UV detection. The methods were determined to be linear, precise and accurate (RSDs were lower than 5%), which allowed the quantitation of β-blockers assayed at concentrations in the range 25-0.78 μg ml⁻¹. After validation of reversed-phase HPLC methods, their analytical error functions were established by a rapid, simple and economical procedure. The discrimination of the best function for each active principle was performed by an appropriate polynomial statistical analysis, yielding SD (μg ml⁻¹) = 0.0295 + 0.0124C − 3.88 × 10⁻⁴C² for celiprolol, 0.0199 + 0.011 C − 1.27 × 10⁻⁵C³ for bisoprolol; and 0.0183 + 0.0089C − 9.68 × 10⁻⁶C³ for oxprenolol. These analytical error functions are an alternative to the weighting methods used in parameter estimation of β-blockers.     

Role of Nanostructures for Anti-proliferation of Bacteria and Their Quantitative Study Validated by Statistical Analysis

The simple and sensitive UV–visible spectrophotometric analytical methods have been adopted for the determination and validation of ZnO nanostructures (nanorods (NRs), nanosphere (NSs), and nanonuts (NNTs)), concentration, which are used to control the bacterial growth of Escherichia coli. This method is based on processing conditions of nanostructures of ZnO using precursors zinc acetate dihydrate (Zn(AC₂)₂·2H₂O), zinc nitrate hexahydrate (Zn(NO₃)₂·6H₂O), sodium hydroxide, hexamethylenetetramine (HMT), methanol, etc. The optical density (OD) of the resulting solution of ZnO nanostructures with E. coli bacteria were measured at 600 nm against the reagent blank, prepared under the same conditions. The use of statistical analysis for evaluation of the resulting solution (ZnO-NRs, ZnO-NSs, and ZnO-NNTs with E. coli) was optimized and validated by various operational parameters. Beer’s law was followed (Concentration range from 0.25–2.0 μg ml^?1) with apparent molar absorptivity of 4.38?×?10² l mol^?1 cm^?1 for ZnO-NRs, 2.70?×?10² l mol^?1 cm^?1 for ZnO-NSs, and 3.10?×?10² l mol^?1 cm^?1 for ZnO-NNTs, respectively. The calibration curve shows linearity over the concentration range of 0.25–1.50 μg ml^?1 for ZnO-NRs and 0.25–2.0 μg ml^?1 for ZnO-NSs and ZnO-NNTs. Detection limit (LOD) and quantitation limit (LOQ) were found to be 0.022:0.068 μg ml^?1 for ZnO-NRs, 0.028:0.087 μg ml^?1 for ZnO-NSs, and 0.044:0.137 μg ml^?1 for ZnO-NNTs analyzed by spectrophotometric method, respectively.     

吡罗昔康两种给药途径的血药浓度与局部浓度比较

探讨和比较了吡罗昔康以口服和透皮两种途径给药后的血药浓度与局部浓度。将小鼠随机分组,分别给予口服混悬剂0.072mg·ml^-1或透皮凝胶剂1mg·g^-1(或2mg·g^-1)。以HPLC法测定小鼠的血药浓度(C_s)和局部浓度(C₁)。结果表明,透皮给药以血药浓度计算凝胶剂的相对生物利用度仅为口服混悬剂的10%。但是透皮给药的C₁/C_s=0.13,远远大于口服给药的C₁/C_s(0.01)。透皮给药后,局部药物浓度—时间曲线下面积为15.85μg·h^-1·ml^-1,远远高于口服给药相应值(1.93μg·h-1·ml^-1)。揭示单纯以血药浓度作为局部作用透皮制剂的生物利用度评价标准是不全面的,应同时考察作用部位的药物浓度。     

A sensitive flow injection chemiluminescence method for the determination of progesterone

A sensitive flow injection (FI) chemiluminescence (CL) method was developed for the determination of trace amounts of progesterone. This method was based on the luminescent properties of the tris(1,10‐phenanthroline) ruthenium(II) ‐ potassium permanganate (KMnO₄) ‐ progesterone in acidic medium sensitized by Na₂SO₃. With the peak height as a quantitative parameter applying optimum conditions, the relative CL intensity was linear with progesterone concentration in the range of 1.0 × 10^?10 ～ 6.0 × 10^?9 g·ml^?1 and 6.0 × 10^?9 ～ 4.0 × 10^?8 g·ml^?1 with a detection limit of 7.1 × 10^?11 g·ml^?1. The relative standard deviation (RSD) was 2.79% for 1.0 × 10^?8 g·ml^?1 progesterone (n = 11). The proposed method held low detection limit and was successfully applied to determination of progesterone in pharmaceutical preparations. The possible CL reaction mechanism was also discussed. Copyright © 2011 John Wiley & Sons, Ltd.     

蛋白激酶抑制剂staurosporine增强抗癌药对肿瘤细胞的杀伤

蛋白激酶抑制剂staurosporine 5 ng·ml^-1阻断人胚肺2BS细胞于G₁/S边界,而不影响人胃癌BGC-823细胞的周期运行。细胞周期时相特异药物阿霉素、阿糖胞苷或博莱霉素A₅与staurosporine合用,2BS细胞和BGC-823细胞的IC₅₀均发生改变,显示低剂量staurosporine增强抗癌药对肿瘤细胞的杀伤。用谷胱甘肽(GSH)的荧光探针mBCL测定不同细胞周期时相的GSH,发现staurosporine使2BS细胞中GSH含量显著增高,而使BGC-823细胞中GSH含量显著下降。Staurosporine对正常和肿瘤细胞周期行进及胞内GSH水平的不同影响,可能是它增强抗癌药物对肿瘤细胞杀伤作用的原因。     

Stereoselective determination of R(−)- and S(+)-prilocaine in human serum using a brush-type chiral stationary phase,solid-phase extraction and UV detection

A chiral HPLC method was developed for the quantitation of R(−)- and S(+)-prilocaine in human serum. The method involves sensitive and selective detection of R(−)- and S(+)-prilocaine using normal-phase chiral HPLC on a pirkle-type naphthyl ethylamine stationary phase (Sumichiral OA-4700, 250 mm × 4 mm i.d.) at ambient temperature with a flow rate of 0.8 ml min⁻¹. A sample clean-up procedure was used for isolation of the analytes of interest from human serum using Bond-Elut C₁₈ columns with high recovery and selectivity. The detection limits were 4 ng ml⁻ for R-prilocaine and 5 ng ml⁻¹ for S-prilocaine. The limits of quantitation were 10 ng ml⁻¹ for both enantiomers. Linear calibration curves in the 10–1000 ng ml⁻¹ range showed good coefficients of determination >0.999 (n − 3). Precision and accuracy of the method were within 4–5.8% and 1.5–4.8% respectively for R(−)-prilocaine, and 2.8–5.7%, and 3.2–5.2% respectively for S(+)-prilocaine.     

Estimation of the area under the concentration-versus-time curve of carboplatin following irinotecan using a limited sampling model

Objectives: The aim of this study was to develop limited sampling models for estimating the area under the concentration-versus-time curve (AUC) of carboplatin. Methods: Based on pharmacokinetic analyses of 14 patients who received 300?mg?·?m² of carboplatin over a 90-min infusion following irinotecan, we developed limited sampling models with stepwise multiple linear regression analysis. We validated these models to be unbiased and precise using pharmacokinetic data of a second group of 14 patients. We also compared the observed and the predicted AUC in the patients using Calvert's formula with the patients' renal function. Results: We developed the following models: AUC (mg?·?ml^?1?·?min)?=?0.784?×?C₄?+?1.30 (r ²?=?0.930) and AUC?=?0.100?×?C_0.25?+?0.597?×?C₄?+?0.140 (r ²?=?0.992), where C_0.25 and C₄ denote unbound plasma concentrations (μg?·?ml^?1) of carboplatin at 0.25?h and 4?h after the end of infusion, respectively. These models were validated to be unbiased and precise: a mean prediction error (MPE) with standard deviation (SD)?=?2.41 (9.45)% and a root mean squared error (RMSE)?=?9.42% for the one-sample model, and MPE with (SD)?=?1.22 (5.56)% and RMSE?=?5.49% for the two-sample model. We also calculated predicted AUC in the patients using Calvert's formula: MPE with (SD) =?5.87 (21.5)% and RMSE =?21.5%. Conclusions: These estimations were, as expected, more accurate than the prediction using Calvert's formula based on patients' renal function. The result of this study confirmed the idea that the pharmacokinetic parameters derived from limited sampling models would be more suitable for pharmacokinetic analysis of carboplatin than those obtained using Calvert's formula.     

(+),(-)和(±)棉酚在雌大鼠抗早孕作用的研究

妊娠第6～9天大鼠,分别ig(±)和(-)棉酚80mg·kg^-1·d^-1和40mg·kg^-1·d^-1,结果有明显的抗早孕作用。然而(+)棉酚40mg·kg^-1·d^-1对大鼠生育无明显影响。(-)棉酚30μg·ml^-1能抑制体外培养黄体细胞孕酮的分泌。(+)棉酚10μg·ml^-1能促进黄体细胞分泌孕酮。hCG1IU·ml^-1能明显刺激体外培养颗粒细胞孕酮的分泌。(±)棉酚10和30μg·ml^-1皆能明显降低颗粒细胞对hCG的反应性。     

高效液相色谱法测定4-[4″-(2″,2″,6″,6″-四甲基哌啶氮氧自由基)氨基]-4'-去甲表鬼臼毒素大鼠血浆浓度及药代动力学参数

建立了大鼠血浆中4-[4″-(2″,2″,6″,6″-四甲基哌啶氮氧自由基)氨基]-4'-去甲表鬼臼毒素(GP-7)浓度的HPLC测定方法。用ODS柱分离,甲醇-水-冰醋酸(59:41:0.6)为流动相,检测波长285nm。血浆甲乙醚-二氯甲烷混合液萃取,45℃水浴蒸干,残渣用流动相溶解进样,内标法定量;血药浓度在2～200μg·ml^-1范围内呈线性关系,r=0.9997,血浆最低检测浓度0.2μg·ml^-1,方法回收率94%～100%,日内、日间RSD2.29%～7.70%。大鼠ivGP-710,20,30mg·kg^-1,药代动力学过程符合二室开放模型,消除半衰期为39.8±10.8min。     

Effects of oblongine chloride,an alkaloid from Leontice leontopetalum on guinea-pig isolated smooth muscle and heart

1. The effects of (−)oblongine chloride, a quaternary alkaloid from Leontice leontopetalum, on guinea-pig isolated ileal longitudinal segments, main pulmonary artery rings, spontaneously-beating atrium and isolated perfused heart were studied.2. Oblongine chloride (3 × 10⁻⁵−10⁻³ M) caused concentration-dependent relaxation of ileum, an effect which was not blocked by propranolol (10⁻⁶ M) alone or in combination with prazosin (3 × 10⁻⁸ M), or by indomethacin (10⁻⁶ M), but was reduced by desensitization of the preparation by prior exposure to 3 × 10⁻⁵ M ATP and, at high concentrations of oblongine, by a combination of propranolol and yohimbine (3 × 10⁻⁶ M).3. Oblongine chloride (10⁻⁵−3 × 10⁻³ M) caused concentration-dependent relaxation of epinephrine-precontracted pulmonary artery. This effect was not affected by propranolol or by indomethacin but was significantly attenuated by pretreatment with 3 × 10⁻⁵ M ATP and potentiated by pretreatment with quinacrine (10⁻⁵ M).4. Oblongine chloride (10⁻⁵M−3 × 10⁻³ M) caused concentration-dependent increase in the contractility but did not affect the rate of the atrium. Similar effects were obtained with isolated perfused heart except that large concentrations of oblongine (10⁻³, 3 × 10⁻³ M) inhibited both contractility and rate of the heart. The inotropic effects of oblongine on the atrium were not blocked by propranolol or indomethacin but were significantly blocked by quinacrine.5. These observations suggest that the effects of oblongine chloride are not mediated by the stimulation of adrenergic receptors on these preparations but are mediated by purinergic receptors and by an interference with the arachidonic acid metabolism but not along the cyclooxygenase pathway.     

双部位吸收模型拟合吉非贝齐在人体中药代动力学数据

测定了8名受试者po吉非贝齐(Gem)600mg后血药浓度一时间数据,观察到血药浓度双峰现象。建立一种双部位吸收药动学模型拟合这些数据,实验值与拟合值吻合好,r²均大于0.99。相应参数如下:T_max1.10±0.46h;T_max32.60±0.73h;C_max113.62±4.3μg·ml^-1);C_max217.22±3.83μg·ml^-1);T₁0.06±0.06h;T₂1.42±0.57h;T₃1.79±0.60h。     

On iontophoretic delivery enhancement: Ionization and mobility of lidocaine hydrochloride in propylene glycol

The structure of lidocaine hydrochloride (LidHCl) in propylene glycol (PG), a solvent known to enhance transdermal delivery of drugs, and the mobilities of the different kinds of ionic species appearing in this system was investigated at 25.0°C by precision conductometry. The molar conductivity was determined at several concentration between 0.4 and 10 mM and the data analysed using the conductance equation of Fuoss-Hsia and Fernandez-Prini (FHFP equation). For concentrations of up to ≈1.2 mM no higher aggregates that LidH⁺ were found. Using a two-parameter analysis of the equilibrium, LidH⁺⇔Lid+H⁺, we obtained the acid dissociation constant, K_a(LidH⁺)=2.5·10⁻⁷ (molar scale); pK_a=6.60, and the limiting molar conductivity, λ₀(LidH⁺)=0.2675 cm²/Ω per mol. For concentrations above 1.2 mM there is strong evidence of formation of ion-pairs, LidH⁺Cl⁻. The ion-pair association constant was estimated to K_p≈40 indicating that about 15% of the electrolyte is in the form of LidH⁺Cl⁻ at the highest concentration (10 mM) investigated.     

腺嘌呤衍生物的合成及体外抗疱疹病毒活性

以腺嘌呤为母体,在其9位引入活性基团N-取代缩氨基硫脲(TSC),设计合成了12个6-氨基-9(N^4'-取代乙醛缩氨基硫脲)嘌呤衍生物(4a～1),并进行了体外抗单纯疱疹病毒I型(HSV-1),II型(HSV-2),水痘-带状疱疹病毒(VZV)活性试验及细胞毒性试验。结果表明,除化合物4e及4f对HSV-1及VZV有较高活性外,其余化合物对上述两种病毒的活性均不明显。另外,将4e与4f分别与无环鸟苷(ACV)联合用药,其最小抑制浓度(MIC)及细胞毒性(MCC)均显著下降。     

高效液相色谱法测定人血清盐酸劳卡尼浓度

介绍了一种测定人血清盐酸劳卡尼(lorcainide hydrochloride)浓度的高效液相色谱法(HPLC)。不锈钢分析柱(200mm×5mmID)固定相为YWG C₁₈H₃₇,5μm颗粒。流动相为甲醇-水-0.625mol·L^-1醋酸铵(86:13:1v/v),用浓氨水调至pH8.0。流速1ml·min^-1。取地尔硫(diltiazem)为内标物。紫外检测波长226nm。低、中、高3种浓度方法回收率分别为95.85%,100.63%,100.09%,由低至高四种浓度日内、日间RSD小于7%。血清最低检测浓度为5μg·L^-1。在20～800μg·L^-1浓度范围内线性良好,r=0.9996。     

Influence of inflammatory disease on the clinical pharmacokinetics of atenolol and metoprolol

The influence of inflammatory disease on the pharmacokinetics of atenolol and metoprolol was investigated after administering single oral 100mg doses of the drugs to six subjects. Each subject had a respiratory tract infection with an erythrocyte sedimentation rate (ESR) of over 20 mm in the first hour and a body temperature of at least 38·5°. Since the subjects subsequently received atenolol and metoprolol when they were healthy, each person acted as his own control. Inflammatory disease had no influence on the kinetics of metoprolol. In contrast, mean peak plasma levels and AUC for atenolol were significantly lower, both by about 40 per cent, during infectious disease compared to the healthy state (p<0·05), where as renal clearance of atenolol slightly increased from 110·8 ± 14·7mlmin^?1 in the healthy state to 128·21·6mlmin^?1, when the ESR's were elevated. The elimination half-life of atenolol, about 10 h, was not affected by the health status of the subjects. Reduced absorption in the gastro-intestinal tract and enhanced elimination of atenolol from plasma might account for the decreased AUC and peak plasma levels of the drug during inflammatory disease.     

HPLC法测定血浆中六亚甲基二乙酰胺浓度

ＨＰＬＣ法测定血浆中六亚甲基二乙酰胺浓度赵玉喜，何晓英，蒋淼，谢景文，谢廷泉，任礼勤（兰州军区总医院药材科，兰州７３００５０）六亚甲基二乙酰胺（ｈｅｘａｍｅｔｈｙｌｅｎｅｂｉｓａｃｅｔａｍｉｄｅ，ＨＭＢＡ）是结构上与二甲基亚砜（ＤＭｓＯ）和Ｎ－甲基甲...     

The offset of β-adrenoceptor antagonism of the responses of the rat right ventricle to isoprenaline

1 The aim of the study was to test the hypothesis that the offset of action of β-adrenoceptor antagonists on the heart is related to their lipophilicity, with low and highly lipophilic drugs having a rapid and slow offset, respectively. The effects of β-blockers with low (atenolol), moderate (celiprolol), high (propranolol) and very high (bopindolol) lipophilicity on the contractile responses of the rat right ventricle to isoprenaline were determined. 2 Atenolol at 10^??6 and 10^??5 m , celiprolol at 10^??7, 10^??6 and 10^??5 m , propranolol at 10^??8, 10^??7 and 10^??6 m and bopindolol at 2 × 10^??9 and 10^??8 m caused parallel rightward shifts of the isoprenaline response curves with no effect on maximum responses. The Schild plots for atenolol, celiprolol and propranolol had slopes that were not significantly different from 1, which is indicative of competitive reversible antagonism. The pK_B values were 7.33, 7.78, and 8.79 for atenolol, celiprolol, and propranolol, respectively. The Schild plot for bopindolol had a slope that was significantly greater than 1. 3 Our hypothesis is supported as the effects of propranolol and bopindolol were more slowly offset than those of atenolol and celiprolol. Thus, the concentration-ratio of 141 in the presence of atenolol at 10^??5 m was reduced to 4 after the first wash, whereas the ratio of 100 in the presence of propranolol at 10^??7 m was only reduced to 45 after a similar wash. The ratio of 54 with celiprolol at 10^??6 m was reduced to 5, whereas the ratio of 70 with bopindolol at 10^??8 m was only reduced to 28 by the first wash. 4 The effects of bopindolol were very slowly or not reversible over two washes in the absence or presence of atenolol at 10^??6 m . It is suggested that bopindolol is a very slowly reversible β-blocker, and that this contributes to its slow offset of action.     

海南粗榧新碱衍生物HH07A的抗肿瘤作用

用细胞生长曲线测定法及软琼脂集落形成分析法研究了HH07A对几种肿瘤及正常细胞生长的影响。结果表明,1.5ug·ml^-1及3μg·ml^-1HH07A能分别明显抑制L1210和HL-60细胞的生长。3种肿瘤细胞对HH07A的敏感性依次为L1210>KB>HL-60,而正常小鼠粒系祖细胞GM-CPC对药物的敏感性则低于前三者,且HH07A3.5μg·ml^-1对HL-60细胞无分化诱导作用。HH07A对腹水型L1210白血病小鼠、S180小鼠均有较明显的治疗作用,使L1210荷瘤小鼠、S180荷瘤小鼠存活时间延长。也能抑制S180实体瘤的生长。     

胶束电动毛细管色谱法分离和测定几种大黄含量

建立了胶束电动毛细管色谱法分离和测定几种大黄中大黄素、芦荟大黄素、大黄酸含量的测定方法。缓冲液为含0.025mol·L^-1十二烷基磺酸钠(简称SDS)的0.025mol,L-13-环己氨基-1-丙烷磺酸(简称CAPS)-乙腈(100:10),pH0.96。线性范围:芦荟大黄素为0.0025～0.0175mg·ml^-1(r=0.9999),大黄素为0.005～0.05mg·ml^-1(r=0.9999),大黄酸为0.005～0.035mg·ml^-1(r=0.9996)。回收率:芦荟大黄素为98.2%～101.8%,大黄素99.9%～101.9%,大黄酸99.2/～101.2%。此法简便、快速、重现性好。     

Spectrophotometric investigation on complex formation of captopril with palladium(II) and its analytical application

The formation of the complex between captopril and palladium(II) chloride in Britton-Robinson buffer solution was studied. It has been established that captopril reacts with palladium(II) chloride in the pH range 2.14–9.10 to form a yellow water — soluble 2:1 complex with maximum absorbance at 380 nm. By applying different spectrophotometric methods, the conditional stability constant of the complex at the optimum pH of 4.03 and ionic strength μ = 0.5 M was found to be 10^8.25. The molar absorptivity was 1.875 × 10³ l mol⁻¹ cm⁻¹. Beer's law was obeyed in concentrations up to 5 × 10⁻⁴ M captopril. The detection limit was 2.17 μg ml⁻¹ and the relative standard deviation varied from 1.24 to 1.68%. The proposed method was found to be suitable for the accurate and reproducible analysis of captopril in water and in tablets.