Comparison of double log-log,mixture response-surface and combined NIBS/Redlich-Kister solubility models

The accuracy and prediction capability of the linear double log-log (LDL-L), mixture response-surface (MR-S) and the combined nearly ideal binary solvent/Redlich-Kister (CNIBS/R-K) solubility equations have been compared using the model parameters calculated from either the whole data or a minimum number of data in an experimental set. The CNIBS/R-K model produced better prediction for some experimental sets than the other two models when the parameters obtained from the whole data in a set were employed, whereas the LDL-L model was superior to the other models when the parameters calculated from a minimum number of data were used, indicating its greatest prediction capability.     

A model to represent solvent effects on the chemical stability of solutes in mixed solvent systems

The applicability of the combined nearly ideal binary solvent/Redlich-Kister (CNIBS/R-K) equation for quantification of solvent effects on the stability of a solute is shown employing the experimental data of three solutes in different aqueous binary solvents. The proposed model provides a simple computational method to correlate/predict the instability rate constant of a drug in mixed solvent systems. The accuracy of the model is compared with that of a model proposed by Connors and co-workers employing various methods including mean percentage deviation (MPD) as comparison criteria. The obtained overall MPD values for the proposed model to correlate and predict the instability rate constants are 2.05 +/- 1.44 and 4.41 +/- 3.21%, respectively, where the corresponding values for Connors' model are 4.34 +/- 3.28 and 10.74 +/- 9.86%. The results suggest that by using only five experimental instability rate constants at different concentrations of the cosolvent in a binary mixture, it is possible to predict unmeasured values falling between data points within an acceptable error range.     

Comparison of various cosolvency models for calculating solute solubility in water-cosolvent mixtures

Previously published cosolvency models are critically evaluated in terms of their ability to mathematically correlate solute solubility in binary solvent mixtures as a function of solvent composition. Computational results show that the accuracy of the models is improved by increasing the number of curve-fit parameters. However, the curve-fit parameters of several models are limited. The combined nearly ideal binary solvent/Redlich-Kister, CNIBS/R-K, was found to be the best solution model in terms of its ability to describe the experimental solubility in mixed solvents. Also resented is an extension of the mixture response surface model. The extension was found to improve the correlational ability of the original model.     

Nociceptin/orphanin FQ prevents the antinociceptive action of paracetamol on the rat hot plate test

Nociceptin/orphanin FQ (N/OFQ) is involved in many behavioural patterns; in particular, it exerts a modulating effect on nociception. Like other proposed antiopiates, nociceptin/orphanin FQ has been shown to have analgesic, hyperalgesic as well as antianalgesic properties. Among the various effects proposed on nociceptive sensitivity at supraspinal level, the antagonistic activity toward morphine analgesia seems to be of interest. Therefore, we decided to investigate whether nociceptin/orphanin FQ and [Arg14, Lys15] nociceptin/orphanin FQ (R-K, a nociceptin analogue) can have the same effect on the analgesia produced by nonopioid analgesics. In this study, we examined the antianalgesic effect of nociceptin/orphanin FQ and its analogue R-K on paracetamol-induced analgesia and evaluated by means of the hot plate test in rats. Nociceptin/orphanin FQ was intracerebroventricularly administered, and, after 5 min, a dose of 400 mg/kg paracetamol was injected intraperitoneally, 30 min before the hot plate test. Nociceptin/orphanin FQ and R-K showed a dose-dependent antagonism on the antinociceptive effect of paracetamol, and the activity of both drugs was significantly reduced by the antagonist [Nphe1] Arg14, Lys15-N/OFQ-NH2 (UFP-101). These data indicate that nociceptin/orphanin FQ and R-K have an antianalgesic effect on the analgesia produced by a nonopioid analgesic drug, like paracetamol, that seems to develop within the brain.     

近红外漫反射光谱法快速测定利福平含量

目的:应用近红外漫反射光谱结合偏最小二乘法(NIR-PLS)对利福平胶囊中利福平(RFP)含量进行测定。方法:采用偏最小二乘法(PLS)建立利福平胶囊中利福平含量的相关模型,并用所建立的模型对预测集样品中利福平含量进行预测。结果:所建定量分析模型回归系数r=0.9525。交互验证均方根误差(RMSECV)为0.0073。预测均方根误差(RMSEP)为0.0077。结论:该方法精确度高,且具有方便快捷、非破坏、无污染、成本低等优点,为药物非破坏性分析提供了一种快捷方法。     

药品中多组份不分离同时分光光度测定进展

评述了药物中多组份同时分光光度测定的近期进展，内容包括双或三波长法、导数光谱法、正交函数法、解联立方程法、最小二乘法、差示分光光度法、化学计量学法和两种方法联用等，涉及２８０种药品，指出了各法优缺点及发展的趋势。     

奇异值分解和主成分回归测定克感敏片三组分

将奇异值分解和主成分回归相结合,首次用于药物的含量测定,采用紫外分光光度法同时测定克感敏片中的非那西丁、氨基比林和咖啡因的含量．其结果明显优于最小二乘法．     

一元回归的影响分析

传统的最小二乘法对每个数据都给以相等的权重,因此,当数据中存在异常点、高杠杆点与强影响点时,回归方程的“稳健性”往往受到影响。本文就一元回归分析中这些点的探查与处理,结合实例予以讨论。     

An LC-MS-MS method for the determination of indinavir, an HIV-1 protease inhibitor, in human plasma

A method for the determination of indinavir (IDV) (L-735 524) in human plasma by LC-MS-MS is discussed, and the validation data is presented. The analyte and internal standard are isolated from plasma by a simple acetonitrile precipitation of plasma proteins followed by centrifugation. LC-tandem mass spectrometry in positive ion, multiple reaction monitoring mode used pairs of ions at m/z of 614/421 for indinavir and 628/421 for internal standard, respectively. The calibration curve had a linear range from 3.0 to 12320 ng/ml when linear least square regression weighing 1/x was applied to the concentration versus peak area plot. The advantages of this method are the fast sample preparation, wide dynamic assay range and quick analysis taking only 5 min for each sample run. The robust nature of this assay has been further verified during routine use over several months involving multiple analysts.     

Measurement of pKa values of newly synthesized heteroarylaminoethanols by CZE

Heteroarylaminoethanol derivates are drugs which affect sympathetic nervous system and are used for medications of hypertensis. In solutions they behave like weak bases and their pK_a values represent important information on their potential biological uptake, pharmacological activity and in vivo biodisponsibility. This article brings the measurement of pK_a values of the series of seven new important heteroarylaminoethanols, compounds with potential vasodilating, β-adrenolytic and antioxidant activity, by capillary zone electrophoresis (CZE) with diode-array detection. It has been shown that capillary zone electrophoresis measurements of pK_a can be easily performed with very small quantities of studied substances, and, due to CZE separation power, the purity of samples is not of key importance. Moreover, the CZE method is fast and reliable, providing that suitable operational conditions are selected. The method is based on the measurement of the effective mobility curves within a suitable pH range and related regression analysis where pK_BH⁺ and electrophoretic mobility of BH⁺ are explicitly involved. The selection of sufficient operational buffers is of key importance for accurate and reproducible results, and, this article brings step by step the consideration procedure involved in this process. Further, this paper brings principles of least square regression analysis of non-linear function corresponding to exact explicit formula for mobility curve of monovalent weak base.     

光谱成像结合偏最小二乘判别法快速鉴别西洋参

目的：应用荧光光谱成像技术对不同市售来源的西洋参饮片及其伪品进行检测,结合偏最小二乘判别法区分其真伪,以期实现西洋参饮片的快速无损鉴别。方法：采用凝视式荧光光谱成像装置,对西洋参、人参、桔梗各30份样品进行了荧光光谱成像,提取了其特征光谱曲线。分别采用全光谱偏最小二乘判别（PLS-DA）与联合区间偏最小二乘判别（siPLS-DA）,对3种药材的光谱数据进行了建模分析。结果：相比于PLS-DA方法,siPLS-DA方法提高了模型质量和精度,其在训练集和验证集的识别率分别达到98.33%和96.67%。结论：所建立的模型精度高、预测性能优异,可实现西洋参饮片的快速无损鉴别。     

盐酸地尔硫(艹卓)延迟缓释微丸组合系统释药行为的研究及其数学解析

目的将两种不同释药规律的微丸按一定比例组合成多单元系统,制备释药时滞约为5h,平稳释约并维持药物浓度至24 h 的盐酸地尔硫(艹卓)延迟缓释微丸胶囊,针对疾病发作的时辰节律性,实现择时释药.方法用非线性最小二乘法模型嵌合通用程序对两种微丸体外释药速率经时过程进行模型嵌合,得到其速率经时方程,按一定比例进行迭加,对初始阶段释药曲线用零级动力学方程拟合,选取线性系数最大比例作为最佳组合比例;再用模型嵌合通用程序对组合系统体外释药速率经时过程进行最佳模型嵌合,并得到速率经时方程。结果确定两种微丸的最佳组合比例,用模型嵌合程序对释药速率经时曲线进行嵌合,效果较好,得到两种微丸及其组合系统的释药速率经时方程,实测值与模型嵌合得到的理论值较接近,表明组合释药行为可用数学方程理论表征.结论对微丸系统释药行为的数学解析结果说明,组合系统的释药行为是可预测的,能更准确地解析和表征组合系统的体外释药行为。     

盐酸地尔硫延迟缓释微丸组合系统释药行为的研究及其数学解析

目的将两种不同释药规律的微丸按一定比例组合成多单元系统，制备释药时滞约为5 h，平稳释药并维持药物浓度至24 h的盐酸地尔硫延迟缓释微丸胶囊，针对疾病发作的时辰节律性，实现择时释药。方法用非线性最小二乘法模型嵌合通用程序对两种微丸体外释药速率经时过程进行模型嵌合，得到其速率经时方程，按一定比例进行迭加，对初始阶段释药曲线用零级动力学方程拟合，选取线性系数最大比例作为最佳组合比例；再用模型嵌合通用程序对组合系统体外释药速率经时过程进行最佳模型嵌合，并得到速率经时方程。结果确定两种微丸的最佳组合比例，用模型嵌合程序对释药速率经时曲线进行嵌合,效果较好，得到两种微丸及其组合系统的释药速率经时方程，实测值与模型嵌合得到的理论值较接近，表明组合释药行为可用数学方程理论表征。结论对微丸系统释药行为的数学解析结果说明,组合系统的释药行为是可预测的，能更准确地解析和表征组合系统的体外释药行为。     

Effect of bupropion SR on specific symptom clusters of depression: analysis of the 31-item Hamilton Rating Scale for depression

Principal component (PC) analysis is a statistical technique that has been used to identify core depression symptoms on the Hamilton Rating Scale for Depression (HAM-D). PC analysis is also a useful method to identify unidimensional scales of the HAM-D that are more sensitive to change following antidepressant treatment. Although there have been previous PC investigations of various versions of the HAM-D, there have been no investigations of the 31-item HAM-D scale or investigations that include subjects administered bupropion SR. We performed a PC analysis on data from 910 outpatients who participated in randomized, double-blind trials evaluating bupropion SR versus placebo for major depression. The goal of our analysis was to 1) identify components (domains) of the 31-item HAM-D and 2) determine patient response to bupropion SR using the domains identified. PC analysis produced a solution comprised of 7 domains of the HAM-D that accounted for approximately 49% of the total variance. Bupropion SR demonstrated a significant reduction (p<.01, least square mean change) in symptoms over placebo on 4 domains (cognitive, retardation, fatigue/interest, and anxiety items).     

FTIR Spectroscopy: A Tool for Quantitative Analysis of Ciprofloxacin in Tablets

A simple, accurate and sensitive spectroscopic method has been proposed for the assay of ciprofloxacin in tablet by least square treatment of fourier transform infrared spectrometric data obtained at the wavenumber corresponding to the carbonyl group centered at 1707 cm^-1. The method involves the extraction of the active ingredient with methanol followed by phosphate buffer pH 6.0. The excipients in the commercial tablet preparation did not interfere with the assay. The specifity, linearity, detection limits, precision and accuracy of the calibration curve, drug extraction, infrared analysis and data manipulation were determined in order to validate the method. Moreover, the statistical results were compared with other methods for quantification of ciprofloxacin.     

An adjusted pharmacokinetic equation for predicting drug levels in vivo based on in vitro square root of time release kinetics

An adjusted pharmacokinetic equation that predicts in vivo plasma drug profiles for controlled release (CR) dosage forms having square root of time drug release kinetics has been derived. The CR hydrogel tablets containing hydroxypropyl methylcellulose (HPMC) were formulated with theophylline and Fast Flo lactose, to produce tablets with HPMC K100MP content of 30% w/w. Plasma profiles in vivo were determined from four male beagle dogs. Tablet gel strength (gamma) was measured as previously reported. Results show drug release in vitro follows square root of time kinetics for the formulation in all media (purified H2O, 0.1 N HCl, and pH 6.8 phosphate buffer). The gamma values were not significantly different (p > 0.05) among the tablets in different dissolution media, with absolute values in DI H2O of 6600 erg/cm3, which is above the minimum threshold value of gamma (approximately 6000 erg/cm3) needed for acceptable in vitro/in vivo correlation. Comparison of predicted and observed plasma profiles in vivo, using the adjusted square root pharmacokinetic equation, showed a better fit of the overall pattern and absolute values of the in vivo data as compared to equations that assume first- or zero-order drug release from the HPMC based tablets. The adjusted square root pharmacokinetic equation can serve as a valuable aid in the design of formulations to yield a desired plasma profile in vivo and provides supporting evidence to the mechanism of drug release in vitro.     

Comparison of FT-NIR transmission and UV-vis spectrophotometry to follow the mixing kinetics and to assay low-dose tablets containing riboflavin

For several years, near-infrared spectroscopy (NIRS) has become an analytical technique of great interest for the pharmaceutical industry, particularly for the non-destructive analysis of dosage forms. The goal of this study is to show the capacity of this new technique to assay the active ingredient in low-dosage tablets. NIR spectroscopy is a rapid, non-destructive technique and does not need any sample preparation. As an example, a binary mixture of microcrystalline cellulose and riboflavin was used to prepare tablets of different weights by direct compression. A prediction model was built by using a partial least square regression fit method. The NIR assay was performed by transmission. The results obtained by NIR spectroscopy were compared with a conventional UV-vis spectrophotometry method. The study showed that tablets can be individually analysed by NIR with high accuracy. It was shown that the variability of this new technique is less important than that of the conventional method which is the UV-vis spectrophotometry.     

基于HPLC指纹图谱结合多种化学模式识别评价生脉饮(党参方)质量

目的：建立多批次生脉饮（党参方） HPLC指纹图谱并采用多种化学计量学分析评价多厂家多批次生脉饮（党参方）的整体质量。方法：采用Ultimate XB-C₁₈色谱柱（4.6 mm×250 mm,5 μm）,流动相为乙腈-0.15%甲酸水溶液,检测波长为260 nm,流速0.8 mL·min^-1,柱温20℃,对多批不同厂家和来源的生脉饮（党参方）制剂进行分析,建立中药色谱指纹图谱,并结合聚类分析、主成分分析与偏最小二乘法判别分析对生脉饮（党参方）质量进行评价。结果：建立了生脉饮（党参方） HPLC指纹图谱,确定了23个共有峰,并指认了其中7个色谱峰;多批次生脉饮（党参方） HPLC指纹图谱的相似度为0.061~0.798;聚类分析与主成分分析结果一致,结合正交偏最小二乘法判别分析发现3类主成分中包含的7个成分峰是造成不同批次生脉饮（党参方）质量差异的主要标志物。在多指标成分定量分析方法学考察结果中,7种指标性成分的加样回收率在97.32%~101.26%,RSD为1.89%~3.56%。结论：不同批次的生脉饮（党参方）之间虽有一定的相关性,但存在质量差异。生脉饮（党参方）检测方法的建立可以为其质量控制及评价提供参考依据,且具有一定的药用开发价值,为其进一步药效及制剂研究奠定基础。