Practical Analytical Approach Research Articles

Ultra-Sensitive Quantification of Corticosteroids in Plasma Samples Using Selective Solid-Phase Extraction and Reversed-Phase Capillary High-Performance Liquid Chromatography/Tandem Mass Spectrometry

Low-dose corticosteroids may provide a favorable benefit/risk ratio for many therapeutic applications. However, the extremely low plasma drug concentrations achieved, in conjunction with the insufficient sensitivity/ selectivity of current analytical methods, renders the evaluation of corticosteroid pharmacokinetics (PK) a significant challenge under such conditions. Furthermore, targeted therapeutic strategies involving administration by inhalation or intraocular injection could result in very low but sustained systemic corticosteroid concentrations, which must be quantified to determine potential side effects. Here we describe a robust method for the ultrasensitive quantification of corticosteroids in plasma samples. This was achieved by the combination of a selective solid-phase extraction (SPE) with a highly sensitive capillary LC (microLC)-MS/MS analysis. SPE washing and elution conditions were optimized so that target drugs are selectively extracted from plasma. By eliminating most undesirable compounds from the sample matrix, this selective SPE procedure enabled a high sample loading volume on the microLC column without compromising chromatographic performance and operational robustness and helped to achieve ultralow detection limits for the corticosteroids in plasma. The effect of microLC separation on the signal-to-noise ratio of corticosteroid peaks in plasma samples was investigated. It was found that with sufficient microLC separation, sensitivity was improved because of a decrease in matrix effects and the removal of endogenous interferences. Detection limits of four clinically important corticosteroids (budesonide, dexamethasone, triamcinolone acetonide, and dexamethasone acetate) ranged from 0.2 to 1 pg/mL in plasma, and linearity was good for all drugs in the range of 5-5000 pg/mL. Accuracy was 88-107% and the variation (CV%) was 2.3-11.1%. A limit of quantification (LOQ) of 5 pg/mL was validated for all four compounds. We applied this method to quantify the low levels of triamcinolone acetonide (TACA) in porcine plasma following suprachoroidal administration, which is necessary to estimate systemic drug exposure resulting from this novel clinical approach for treating inflammatory diseases of the eye. TACA in plasma could be quantified at low pg/mL levels for up to 90 days posttreatment. To our knowledge, this is the first practical analytical approach that can monitor plasma corticosteroids after intraocular administration, given the ultralow plasma concentrations achieved. In summary, this strategy enables PK analysis of corticosteroids in treatment regimens that result in extremely low systemic concentrations, and the approach can be extended for the sensitive quantification of other drugs.

Confidence intervals for optimal selection among alternatives with stochastic variable costs

Traditional breakeven analysis assumes that the total cost curve is a linear function of fixed and variable costs, and the intersection of the cost curves or cost and revenue curves provides the optimal solution. The traditional approach is extended to a more realistic treatment by recognizing the uncertainty associated with the variable cost components: that variable costs have a random component and unit variable costs can be random variables, and a practical analytical approach for determining the probability of an alternative being the low-cost alternative at any production volume is presented.

Mayfield Logistic Regression: A Practical Approach for Analysis of Nest Survival

Mayfield Logistic Regression: A Practical Approach for Analysis of Nest Survival

Mayfield Logistic Regression: A Practical Approach for Analysis of Nest Survival

Abstract Mayfield logistic regression is a method for analyzing nest-survival data that extends the traditional Mayfield estimator by incorporating explanatory variables (e.g. habitat structure, seasonal effects, or experimental treatments) in a logistic-regression analysis framework. Although Aebischer (1999) previously showed that logistic regression can be used to fit Mayfield models, few ornithologists have put that finding into practice. My purpose here is to reintroduce this underused method of nest-survival analysis, to compare its performance to that of a dedicated survival-analysis program (MARK), and to provide a practical guide for its use. Like the traditional Mayfield method, Mayfield logistic regression accounts for the num ber of “exposure days” for each nest and allows for uncertain fates (censoring), thus avoiding the bias introduced by typical applications of logistic regression. Mayfield logistic regression should be widely applicable when nests are found at various stages in the nesting cycle and multiple explanatory variables influencing nest survival are of interest.

MODAL DISPERSION CHARACTERISTICS AND WAVEGUIDE DISPERSION OF AN OPTICAL WAVEGUIDE HAVING A NEW UNCONVENTIONAL CORE CROSS-SECTION

In this article, we present a simple and practical analytical approach based on scalar wave approximation to estimate the modal dispersion characteristics and cutoff condition of an optical waveguide having an arbitrary and uniform core cross-section. This structure represents the core of a circular waveguide which is compressed at both the ends of a diameter. We choose the new and appropriate orthogonal coordinates for the proposed waveguide structure and impose the boundary conditions under the weak guidance approximation to get the modal eigen value equation. Using this equation, we achieve numerical results in the form of dispersion curves and cutoff frequencies. Further, representing the normalised frequency parameter as V and normalised propagation constant as b′, the dependence of d(Vb′)/dV on V has been obtained and shown graphically. A brief comparison of the proposed waveguide and the circular waveguide has also been made in respect of the number of sustained modes and waveguide dispersion.

Weather Derivatives and Weather Insurance: Concept, Application, and Analysis

The concept and applications of weather derivatives and weather insurance are introduced. Proper analysis of these financial instruments requires both statistical knowledge and thorough understanding of the physical weather and climate process. A simple but practical analysis approach is developed based on historical data and seasonal forecast. It is then applied to a single and a portfolio of weather derivative contracts. Business implications of the results from the analysis are discussed.

Applicability of Sharp‐Interface Models for NAPL Transport: 2. Spreading of a LNAPL

AbstractThis paper, the second in a two‐part series, examines the applicability of the sharp‐interface approach to modeling initial accumulation and spreading of a light nonaqueous phase liquid (LNAPL) in the ground‐water aquifer. The sharp‐interface approach models NAPL transport by developing a time‐distance profile from Darcy's law by assuming a piston or plug flow. The approach is tested here against an immiscible‐phase model that includes capillarity effects in the formulation. Although significant assumptions are included in the sharp‐interface model, it may be useful for initial screening, in obtaining an order‐of‐magnitude estimate of travel times, and in describing the approximate extent of the free and dissolved NAPL contamination. In the absence of data for calibration, the paper introduces guidelines for estimating the parameters of the model. By integrating the formulation in Part 1 and this part, a practical approach for analysis of NAPL contamination is defined; the underlying assumptions and simplifications have to be recognized, however.