Novel assays for quality evaluation of XueBiJing: Quality variability of a Chinese herbal injection for sepsis management

XueBiJing is an intravenous five-herb injection used to treat sepsis in China. The study aimed to develop a liquid chromatography-tandem mass spectrometry (LC-MS/MS)- or liquid chromatography-ultraviolet (LC-UV)-based assay for quality evaluation of XueBiJing. Assay development involved identifying marker constituents to make the assay therapeutically relevant and building a reliable one-point calibrator for monitoring the various analytes in parallel. Nine marker constituents from the five herbs were selected based on XueBiJing's chemical composition, pharmacokinetics, and pharmacodynamics. A selectivity test (for “similarity of response”) was developed to identify and minimize interference by non-target constituents. Then, an intercept test was developed to fulfill “linearity through zero” for each analyte (absolute ratio of intercept to C response, <2%). Using the newly developed assays, we analyzed samples from 33 batches of XueBiJing, manufactured over three years, and found small batch-to-batch variability in contents of the marker constituents (4.1%–14.8%), except for senkyunolide I (26.5%).     

Refractive indices for volatile anesthetic gases: Equipment and method for calibrating vaporizers and monitors

Objective. The objective of our study was to establish the refractive indices and the virial coefficients of the volatile anesthetic vapors. These indices and coefficients will allow refractometry to be used by manufacturers to produce accurate calibration, without requiring expensive high-precision calibration gases.Methods. We used a precision refractometer to measure the refractive indices for five volatile anesthetic vapors. We prepared our calibration gases by mixing a gravimetrically calibrated amount of liquid agent with a constant gas flow.Results. The refractive indices for the volatile anesthetic vapors are 1,603.2 for halothane, 1,540.4 for enflurane, 1,563.3 for isoflurance, 1,538.3 for sevoflurane, and 1,211.7 for desflurane. The maximum theoretical error in our measurements, due to all sensors and all uncertainty in our measurement of apparatus and physical constants, is ±0.56% of the reading (±0.70% for desflurane).Conclusions. If refractometry replaced calibration gases in cylinders, as a calibration standard, manufacturers might avoid errors that now occur because calibration gases manufactured by numerous companies seem to differ. We propose that our values serve as an interim database.     

A novel multivariate approach using science-based calibration for direct coating thickness determination in real-time NIR process monitoring

This study demonstrates an approach, using science-based calibration (SBC), for direct coating thickness determination on heart-shaped tablets in real-time. Near-Infrared (NIR) spectra were collected during four full industrial pan coating operations. The tablets were coated with a thin hydroxypropyl methylcellulose (HPMC) film up to a film thickness of 28 μm. The application of SBC permits the calibration of the NIR spectral data without using costly determined reference values. This is due to the fact that SBC combines classical methods to estimate the coating signal and statistical methods for the noise estimation. The approach enabled the use of NIR for the measurement of the film thickness increase from around 8 to 28 μm of four independent batches in real-time. The developed model provided a spectroscopic limit of detection for the coating thickness of 0.64 ± 0.03 μm root-mean square (RMS). In the commonly used statistical methods for calibration, such as Partial Least Squares (PLS), sufficiently varying reference values are needed for calibration. For thin non-functional coatings this is a challenge because the quality of the model depends on the accuracy of the selected calibration standards. The obvious and simple approach of SBC eliminates many of the problems associated with the conventional statistical methods and offers an alternative for multivariate calibration.     

Calibration plots for risk prediction models in the presence of competing risks

A predicted risk of 17% can be called reliable if it can be expected that the event will occur to about 17 of 100 patients who all received a predicted risk of 17%. Statistical models can predict the absolute risk of an event such as cardiovascular death in the presence of competing risks such as death due to other causes. For personalized medicine and patient counseling, it is necessary to check that the model is calibrated in the sense that it provides reliable predictions for all subjects. There are three often encountered practical problems when the aim is to display or test if a risk prediction model is well calibrated. The first is lack of independent validation data, the second is right censoring, and the third is that when the risk scale is continuous, the estimation problem is as difficult as density estimation. To deal with these problems, we propose to estimate calibration curves for competing risks models based on jackknife pseudo‐values that are combined with a nearest neighborhood smoother and a cross‐validation approach to deal with all three problems. Copyright © 2014 John Wiley & Sons, Ltd.     

Study of mycotoxin calibration approaches on the example of trichothecenes analysis from flour

The aim of this study was to evaluate the applicability of different calibration approaches in trichothecenes analysis from wheat flour. Concretely eight trichothecenes (five type B trichothecenes and three type A trichothecenes) were analyzed by matrix solid-phase dispersion (MSPD) and liquid chromatography–tandem mass spectrometry (LC–MS/MS). In the first set of experiments the presence of matrix effects was evaluated; values ranged between 59% and 79%. In the second set of experiments, solutions to compensate these signal suppressions were examined. Different calibration methods showed to tackle matrix effects obtaining values between 69% and 85% for external matrix matched calibration and values from 76% to 111% and from 78% to 108% by analog and deuterated internal standard calibrations, respectively. Trueness of the method was studied using quality control material and certificated reference material (DON 1062 ± 110 μg kg⁻¹). The values were compared by matrix-matched, analog internal standard (deepoxydeoxynivalenol (DOM-1)) and deuterated internal standard (DON-d₁).     

Contrasted patterns of hyperdiversification in Mediterranean hotspots

Dating the Tree of Life has now become central to relating patterns of biodiversity to key processes in Earth history such as plate tectonics and climate change. Regions with a Mediterranean climate have long been noted for their exceptional species richness and high endemism. How and when these biota assembled can only be answered with a good understanding of the sequence of divergence times for each of their components. A critical aspect of dating by using molecular sequence divergence is the incorporation of multiple suitable age constraints. Here, we show that only rigorous phylogenetic analysis of fossil taxa can lead to solid calibration and, in turn, stable age estimates, regardless of which of 3 relaxed clock-dating methods is used. We find that Proteaceae, a model plant group for the Mediterranean hotspots of the Southern Hemisphere with a very rich pollen fossil record, diversified under higher rates in the Cape Floristic Region and Southwest Australia than in any other area of their total distribution. Our results highlight key differences between Mediterranean hotspots and indicate that Southwest Australian biota are the most phylogenetically diverse but include numerous lineages with low diversification rates.     

铱192后装放射源在空气中刻度的散射因子

目的:研究铱192后装放射源在空气中刻度的散射因子。方法:PTW井形电离室放置在离地1 m高的支架上,测量在电离室外缘离墙距离5 cm到200 cm处进行,读数以200 cm处读数归一。按多步法、DGMP法和遮挡法要求在空气中用Farmer指形电离室在不同源室距(SCD)上对铱192后装放射源进行测量,遮挡法测量中在放射源和电离室之间放置6 cm厚度的圆锥台型铅挡,测得数据用Origin8.0软件进行拟合处理分析。测量中读数均摈弃端效应、暗电流并做梯度修正。结果:井形电离室对铱192放射源刻度,读数在电离室和墙壁距离较近时受到墙面散射影响,电离室外缘离墙壁距离在1 m以上时散射影响可以忽略,Farmer指形电离室在空气中测量结果表明用Goetsch法和DGMP法计算,散射因子恒定与测量距离(SCD)无关且可以忽略,SF法的散射因子略小。结论:井形电离室刻度后装放射源需在最小散射情况下进行,在空气中用指形电离室进行刻度应对散射进行实际测量,遮挡法是较为符合实际的测量方法。     

Shrinkage estimation and the use of additional information when calibrating in the presence of random effects

Let x denote a precise measurement of a quantity and Y an inexact measurement, which is, however, less expensive or more easily obtained than x. We have available a calibration set comprising clustered sets of (x,Y ) observations, obtained from different sampling units. At the prediction step, we will only observe Y for a new unit, and we wish to estimate the corresponding unknown x, which we denote by ξ. This problem has been treated under the assumption that x and Y are linearly related. Here, we expand on those results in three directions: First, we show that if we center ξ about a known value c, for example, the mean x‐value of the calibration set, then the proposed estimator now shrinks to c. Second, we examine in detail the performance of the estimator, which was proposed when one or more (x,Y ) observations can be obtained for the new subject. Third, we compare the Fieller‐like confidence intervals, previously proposed, with t‐like intervals based on asymptotic moments of the point estimate. We illustrate and evaluate our procedures in the context of a data set of true bladder‐volumes (x) and ultrasound measurements (Y). Copyright © 2013 John Wiley & Sons, Ltd.     

国家对照品氨曲南的协作标定

目的协作标定氨曲南对照品。方法采用高效液相色谱法,色谱柱分别为Lichrospher C18(250mm×4.6mm),Synergi4μFusion-RP80A(250mm×4.6mm),以水-甲醇(80:20)配制的含0.005mol.L-1辛烷磺酸钠和0.02mol.L-1磷酸二氢钾,并用磷酸调节pH至2.6的溶液为流动相,流速为1.0mL.min-1,检测波长为206nm,柱温分别为40℃、30℃,2人分别独立实验。结果含量均值为94.46%,RSD为0.6%。结论选取不同实验室协作标定,所得结果客观真实,系统误差小。     

多波长单因变量偏最小二回归校正法在他莫昔芬高效液相定量分析中的应用

使用偏最小二回归校正法处理他莫昔芬高效液相定量分析数据得到他莫昔芬的多波长标准方程,并将其与传统的单波长标准方程进行比较。结果显示多波长标准方程的平方相关系数大于单波长标准方程的平方相关系数,而多波长标准方程预测标准误小于单波长标准方程。