Method For Direct Measurement Research Articles

Examining Oxygen Saturation and Peak Volume Correlation in Respiratory Disorders: A Study at PCM/PCA Ciledug

Examining Oxygen Saturation and Peak Volume Correlation in Respiratory Disorders: A Study at PCM/PCA Ciledug

Electrocaloric response enhancement over a broad temperature range in lead-free BT-based ceramics

The electrocaloric effect (ECE) capabilities of environmentally sustainable BaTiO3 systems have garnered extensive scrutiny for their potential applications, owing to their intricate phase transition characteristics, facile miniaturization, heightened efficacy, and low cost. Nevertheless, persistent challenges loom in the quest for a substantial trade-off between significant temperature change (ΔT) and a wide operating temperature range (Tspan). In this study, we synthesized the Ba(1–1.5x)LaxTi0.9Zr0.1O3 (abbreviated as BLZT100x, x = 0, 0.005, 0.01, and 0.015) ferroelectric system and conducted thorough characterizations encompassing phase structure, electrical attributes, and electrocaloric properties. The results reveal a reduction in the phase transition temperature to lower regimes and an augmentation in the diffuse phase transition characteristics upon the incorporation of La3+ into the Ba(Zr, Ti)O3 matrix. This enhancement significantly bolsters the electrocaloric performance while expanding the viable operating temperature ranges. Notably, in the BLZT0.5 sample, an exceptional ΔT of 1.22 K under a moderate electric field of 50 kV/cm is observed, accompanied by an extraordinarily broad Tspan of 80 °C spanning from 60 °C to 140 °C, as determined through direct measurement method. These findings impeccably align with the prerequisites of practical refrigeration applications.

Forward solution of shield tunneling pose based on the Newton–Raphson method

To achieve precise control of the shield tunneling pose, obtaining a real-time shield pose state during the excavation process is necessary to achieve closed-loop feedback control of the shield pose. This study proposes a forward solution method to address the high cost and low efficiency of direct measurement methods, such as using lasers and gyroscopes, for measuring shield pose. This method relies on the real-time measurement of the strokes of hydraulic thrust cylinders during shield tunneling. Based on the inverse kinematics of the shield machine, the Newton–Raphson method was used to calculate the shield tunneling pose. Accordingly, a forward solution algorithm for shield pose was developed using MATLAB, and the effectiveness of the proposed method was verified through an example analysis. The results demonstrated the high computational efficiency of the method, proving its potential application in real-time control systems for shield tunneling poses.

Simultaneous Reconstruction of Multiple Time-Varying Thermal Properties Based on Translucent Materials.

In the realm of high-tech materials and energy applications, accurately measuring the transient heat flow at media boundaries and the internal thermal conductivity of materials in harsh heat exchange environments poses a significant challenge when using conventional direct measurement methods. Consequently, the study of photothermal parameter reconstruction in translucent media, which relies on indirect measurement techniques, has crucial practical value. Current research on reconstructing photothermal properties within participating media typically focuses on single-objective or time-invariant properties. There is a pressing need to develop effective methods for the simultaneous reconstruction of time-varying thermal flow fields and internal thermal conductivity at the boundaries of participating media. This paper introduces a computational model based on the numerical simulation theory of internal heat transfer systems in participating media, stochastic particle swarm optimization algorithms, and Kalman filter technology. The model aims to enable the simultaneous reconstruction of various thermal parameters within the target medium. Our results demonstrate that under varying levels of measurement noise, the inversion results for different target parameters exhibit slight oscillations around the true values, leading to a reduction in reconstruction accuracy. However, overall, the model demonstrates robustness and accuracy in ideal conditions, validating its effectiveness.

Sideslip Angle Estimation for Distributed Drive Electric Vehicles Based on Robust Unscented Particle Filter

An accurate and reliable sideslip angle is crucial for active safety control systems and advanced driver-assistance systems (ADAS). The direct measurement method of the sideslip angle suffers from challenges of high costs and environmental sensitivity, so sideslip angle estimation has always been a significant research issue. To improve the precision and robustness of sideslip angle estimation for distributed drive electric vehicles (DDEV) in extreme maneuvering scenarios, this paper presents a novel robust unscented particle filter (RUPF) algorithm based on low-cost onboard sensors. Firstly, a nonlinear dynamics model of DDEV is constructed, providing a theoretical foundation for the design of the RUPF algorithm. Then, the RUPF algorithm, which incorporates the unscented Kalman filter (UKF) to update importance density and utilizes systematic random resampling to mitigate particle degradation, is designed for estimation. Eventually, the availability of the proposed RUPF algorithm is validated on the co-simulation platform with non-Gaussian noises. Simulation results demonstrate that RUPF algorithm attains a higher precision and stronger robustness compared with the traditional PF and UKF algorithms.

Measurement of glomerular filtration rate in patients undergoing renal surgery for cancer: eGFR vs mGFR in the era of precision medicine.

In the era of precision medicine, determining reliable renal function assessment remains a critical and debatable issue, especially in nephrology and oncology. This paper delves into the significance of accurately measured Glomerular Filtration Rate (mGFR) in clinical practice, highlighting its essential role in guiding medical decisions and managing kidney health, particularly in the context of renal cancer (RC) patients undergoing nephrotoxic anti-cancer drugs. The limitations and advantages of traditional GFR estimation methods, primarily using serum biomarkers like creatinine and cystatin C, are discussed, emphasizing their possible inadequacy in cancer patients. Specifically, newer formulae designed for GFR estimation in cancer patients may not perform at best in RC patients. The paper explores various methods for direct GFR measurement, including the gold standard inulin clearance and alternatives like iohexol plasma clearance. Despite the logistical challenges of these methods, their implementation is crucial for accurate renal function assessment. The paper concludes by emphasizing the need for continued research and innovation in GFR measurement methodologies to improve patient outcomes, particularly in populations with complex medical needs.

Efficient Method for Identifying Key Errors Based on 21-Geometric-Error Measurement of Three Linear Axes of Machine Tools

Key errors of machine tools have a significant impact on their accuracy, however accurately and quickly measuring the geometric errors of machine tools is essential for key error identification. Fortunately, a quick and direct laser measurement method and system for 21 geometric errors of three linear axes of machine tools were proposed previously, which enables the measurement of all 21 geometric errors via a one-step installation and a three-step automated measurement process. Based on this, to efficiently identify the key error factors, this paper first utilizes the 21 geometric errors obtained from the proposed measurement system to evaluate the contribution of each error to the volumetric errors of machine tools, leading to the building of a 21-geometric-error sensitivity analysis model. Then, experiments are carried out on the vertical machining tool TH5656, and all 21 geometric errors are obtained in 5 min. After this, the volumetric error distribution in the machining workspace is mapped according to the relationship between the geometric errors and the machining errors, and the key error factors affecting the manufacturing and machining accuracy of the TH5656 are ultimately determined. Thus, this new method provides a way to quickly identify key errors of the three linear axes of machine tools, and offers guidance for the machine tool configuration design, machining technology determination, and geometric error compensation.

Wall shear stress measurement using a zero-displacement floating-element balance

The floating-element (FE) principle, introduced nearly a century ago, remains one of the most versatile direct wall shear stress measurement methods. Yet, its intrinsic sources of systematic error, associated with the flow-exposed gap, off-axis load sensitivity, and calibration, have thus far limited its widespread application. In combination with the lack of standard designs and testing procedures, measurement reliability still hinges heavily on individual judgement and expertise. This paper presents a framework to curb these limitations, whereby the design and operation of a FE balance are leveraged by an analytical model that attempts to capture the behaviour and predict the relative contribution of the systematic sources of error. The design is based on a parallel-shift linkage and a zero-displacement force-feedback system. The FE has a surface area of 200×200\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$200\ imes 200\\,$$\\end{document} mm, and measurement sensitivity is adjustable depending on the surface condition and the Reynolds number. It is thus suitable for application in a wide range of low-speed, boundary-layer wind tunnels, small or large scale. Measurements of the skin friction coefficient over a smooth wall show a remarkable agreement with oil-film interferometry, especially for Reθ>1.3×104\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$${\\rm Re}_{\ heta } > 1.3 \ imes 10^4$$\\end{document}. The discrepancy relative to the empirical Coles–Fernholz relation (κ=0.39\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\kappa = 0.39$$\\end{document} and C=4.352\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$C = 4.352$$\\end{document}) is within 0.5\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$0.5\\,$$\\end{document}%, and the level of uncertainty is below 1\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$1\\,$$\\end{document}% for a confidence interval of 95\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$95\\,$$\\end{document}%.

Study on assessing the impact of evaporation on the natural recharge in the Holocene aquifer of sand dunes in Ben Tre province, Vietnam

On the surface of the terrain in Ben Tre province, sand dunes exist in the form of thin strips running parallel and facing the coastline, with a total distributed area of about 12,179 hectares. These sand dunes vary in size, with widths ranging from 100 to 620 meters and lengths from 1,200 to 7,200 m. The predominant geological component in these sand dunes is fine-grained sand with large pore sizes. The vegetation cover on these sand dunes is sparse, with numerous hours of sunlight throughout the year. The air temperature and surface evaporation are high, creating favourable conditions for the evaporation process from the groundwater surface. This study employs the direct evaporation measurement method using Lysimeter (LS) based on the water balance principle. The LS measuring station is located in Tan Thuy commune, Ba Tri district, Ben Tre province, to monitor the groundwater loss through evaporation, simulating real conditions with groundwater levels at depths of 0.5 and 0.9 m. The monitoring and calculations show that the total groundwater evaporation during the period from 1 June 2022 to 31 May 2023 is approximately 142.5 mm, equivalent to 24.9% of the natural recharge of the aquifer.

Experimental study on the aerodynamic characteristics of combined angle transmission tower subject to skew wind

The transmission towers served as crucial carriers in the process of power transmission. The combined angle transmission tower of dual-angle steel with cruciform section are relatively a novel type of angle tower, which is being more widely used in transmission lines. The studies on aerodynamic characteristics of combined angle tower in skewed wind are limited. In this paper, the wind tunnel tests are conducted to investigate the aerodynamic characteristics of the combined angle tower, and the high frequency force balance (HFFB) test is introduced to obtain the transverse and longitudinal forces on the tower using the direct force measurement (DFM) method. The drag coefficients and wind load-distribution factors of the combined angle tower are obtained from the wind tunnel tests, and the effects of interference and tower leg spacing on the wind loads of the tower legs are fully explored. It can be found that the aerodynamic coefficients and drag coefficients of the combined angle steel tower leg tend to decrease with the increase of interference members and it also decreases with the decrease of the tower leg spacing. The test wind load-distribution factors of the isolated leg are generally larger than those defined by seven typical codes (e.g., US, EU, Japanese, and Chinese codes) and significantly exceed the code-specified values under partial wind angles. The observations obtained from this study may provide helpful guidance on the wind-resistant design of this relatively novel type of combined angle tower.

Establishment of the deuterium oxide dilution method as a new possibility for determining the transendothelial water permeability.

Increase in transendothelial water permeability is an essential etiological factor in a variety of diseases like edema and shock. Despite the high clinical relevance, there has been no precise method to detect transendothelial water flow until now. The deuterium oxide (D2O) dilution method, already established for measuring transepithelial water transport, was used to precisely determine the transendothelial water permeability. It detected appropriate transendothelial water flow induced by different hydrostatic forces. This was shown in four different endothelial cell types. The general experimental setup was verified by gravimetry and absorbance spectroscopy. Determination of transendothelial electrical resistance (TEER) and immunocytochemical staining for proteins of the cell-cell contacts were performed to ensure that no damage to the endothelium occurred because of the measurements. Furthermore, endothelial barrier function was modulated. Measurement of transendothelial water flux was verified by measuring the TEER, the apparent permeability coefficient and the electrical capacity. The barrier-promoting substances cyclic adenosine monophosphate and iloprost reduced TEER and electrical capacity and increased permeability. This was accompanied by a reduced transendothelial water flux. In contrast, the barrier-damaging substances thrombin, histamine and bradykinin reduced TEER and electrical capacity, but increased permeability. Here, an increased water flow was shown. This newly established in vitro method for direct measurement of transendothelial water permeability was verified as a highly precise technique in various assays. The use of patient-specific endothelial cells enables individualized precision medicine in the context of basic edema research, for example regarding the development of barrier-protective pharmaceuticals.

Evaluation method for the impact of digital finance on the environmental performance of manufacturing industry

ABSTRACT A new evaluation method for the impact of digital finance on the environmental performance of the manufacturing industry is proposed to improve the accuracy of evaluation results and provide reliable data for enterprise development. Establish a scientific and comprehensive evaluation index system that includes environment, cost-effectiveness, life cycle, and sustainable development. Collect sample data through indirect measurement and direct measurement methods through questionnaire surveys and standardize each data through the measurement of digital economy development level to eliminate differences between different indicators. Based on the constructed evaluation indicator system and sample data collection results, the weights of each evaluation indicator are determined by establishing a projection pursuit model. The fuzzy comprehensive evaluation method and the analytic hierarchy process are used to obtain the fuzzy comprehensive evaluation results of environmental performance based on the projection pursuit model to evaluate the impact of digital finance on the environmental performance of the manufacturing industry. The experimental results show that compared with traditional business models, digital business models can effectively reduce energy consumption, operating costs, and logistics transportation costs of enterprises, improve resource utilization efficiency, and outperform traditional methods in evaluation accuracy, recall rate, and efficiency, verifying the effectiveness of this method.

Mechanical strength measurement of needle-shaped CaSO4 microcrystals by a three-point bend test

A simple method for direct measurement of the mechanical strength of needle-shaped microcrystals of calcium sulfate, CaSO4, is proposed. The microcrystals, with a length from 30 to 50 μm and transverse dimensions from 1 to 3 μm, can act as reinforcing filler in various structural and building composites to improve their mechanical properties. The method is based on a three-point bend test, adapted to microscopic objects. The CaSO4 microcrystals were placed on a substrate, which was a twill-weave filter mesh consisting of intertwined steel fibers with diameter of ∼25 μm. Due to the twill weave, the mesh surface is characterized by a periodic distribution of protrusions and depressions. The protrusions act as supports for the placing of microcrystals, and the depressions provide the possibility of deformation and destruction of microcrystals under the action of an increasing vertically acting force, which is applied to the microcrystal through the indenter of the dynamic ultra-micro hardness tester. The moment of destruction of the microcrystals is observed to be dependent on the force on the displacement of the indenter. The measured values of the mechanical strength of CaSO4 microcrystals varied in a range from ∼3.5 to ∼6.0 GPa. The experimental strength values are in good agreement with the values obtained from the results of numerical analysis of the stressed state formed in the volume of CaSO4 microcrystals during the three-point bend test.

Comparing the performance of machine learning methods in estimating the shear wave transit time in one of the reservoirs in southwest of Iran.

Shear wave transit time is a crucial parameter in petroleum engineering and geomechanical modeling with significant implications for reservoir performance and rock behavior prediction. Without accurate shear wave velocity information, geomechanical models are unable to fully characterize reservoir rock behavior, impacting operations such as hydraulic fracturing, production planning, and well stimulation. While traditional direct measurement methods are accurate but resource-intensive, indirect methods utilizing seismic and petrophysical data, as well as artificial intelligence algorithms, offer viable alternatives for shear wave velocity estimation. Machine learning algorithms have been proposed to predict shear wave velocity. However, until now, a comprehensive comparison has not been made on the common methods of machine learning that had an acceptable performance in previous researches. This research focuses on the prediction of shear wave transit time using prevalent machine learning techniques, along with a comparative analysis of these methods. To predict this parameter, various input features have been employed: compressional wave transit time, density, porosity, depth, Caliper log, and Gamma-ray log. Among the employed methods, the random forest approach demonstrated the most favorable performance, yielding R-squared and RMSE values of 0.9495 and 9.4567, respectively. Furthermore, the artificial neural network, LSBoost, Bayesian, multivariate regression, and support vector machine techniques achieved R-squared values of 0.878, 0.8583, 0.8471, 0.847 and 0.7975, RMSE values of 22.4068, 27.8158, 28.0138, 28.0240 and 37.5822, respectively. Estimation analysis confirmed the statistical reliability of the Random Forest model. The formulated strategies offer a promising framework applicable to shear wave velocity estimation in carbonate reservoirs.

Modelling and Thermographic Measurements of LED Optical Power.

This paper presents a simple engineering method for evaluating the optical power emitted by light-emitting diodes (LEDs) using infrared thermography. The method is based on the simultaneous measurement of the electrical power and temperature of an LED and a heat source (resistor) that are enclosed in the same plastic packaging under the same cooling conditions. This ensures the calculation of the optical power emitted by the LED regardless of the value of the heat transfer coefficient. The obtained result was confirmed by comparing it with the standard direct measurement method using an integrated sphere. The values of the estimated optical power using the proposed method and the integrated sphere equipped with a spectrometer were consistent with each other. The tested LED exhibited a high optical energy efficiency, reaching approximately η ≈ 30%. In addition, an uncertainty analysis of the obtained results was performed. Compact modelling based on a thermal resistor network (Rth) and a 3D-FEM analysis were performed to confirm the experimental results.

Electrocaloric effect near room temperature in lead-free Aurivillius phase Sr2Bi4Ti5O18 upon La and Nb codoping

La and Nb codoping of ferroelectric five-layer Aurivillius phase Sr2Bi4Ti5O18 (TC ∼ 560 K), induces compositional disorder and diffuse relaxor transitions at much lower temperatures than the parent compound, while preserving the orthorhombic structure. For moderate La and Nb concentrations, the ferroelectric properties are enhanced in the vicinity of room temperature, and so is the electrocaloric effect as measured directly with a homemade quasi-adiabatic calorimeter. The adiabatic temperature change reaches, e.g., in Sr2Bi3.44La0.5Ti4.8Nb0.2O18, ΔT ⁓ 0.3 K at 355 K with a temperature span ⁓ 15 K, under ΔE = 37 kV/cm. Besides, a large field dispersion of the electrocaloric effect is found, ascribed to field-induced transitions from short-range-ordered relaxor to long-range-ordered ferroelectric states. Indirect estimations of the electrocaloric effect from electric polarization data are not able to quantitatively predict the direct results and emphasize the need of applying direct measurement methods, especially for relaxor ferroelectrics.

Thermal relaxation parameters estimation of non-Fourier heat transfer in laser-irradiated living tissue using the Levenberg-Marquardt algorithm

The present work is concerned with solving the inverse heat transfer problem (IHTP) to estimate the thermal relaxation parameters corresponding to the dual phase lag (DPL) model-based bio-heat transfer in laser-irradiated living tissue. This problem is divided into two parts: direct and inverse problems. The solution of the inverse problem has been obtained using the Levenberg–Marquardt algorithm. On the other hand, the solution to the direct problem is obtained by solving the DPL model-based bio-heat transfer equation (BHTE) with the transient radiative transfer equation (TRTE). So, the TRTE has been numerically solved by the modified discrete ordinate method (DOM) to find the intensity field in the living tissue subjected to short-pulsed laser radiation, and it acts as a heat source in the DPL model-based BHTE. So, the DPL model-based BHTE has been analytically solved by employing the finite integral transform technique to get the temperature variation inside the laser-irradiated living tissue. First, the computer code developed for estimating unknown thermal relaxation parameters using the Levenberg–Marquardt algorithm has been verified against the data given in the literature, and found good agreement between them. Then, the thermal response of laser-irradiated living tissue has been investigated. After that, the influence of sensor position on the sensitivity of the IHTP solution has been discussed. The impact of the total transient readings and the measurement error on estimating the unknown parameters have been investigated. The present study’s findings can significantly contribute to various parameter estimation problems where the conventional methods for direct measurements of parameters are impossible or very difficult. Furthermore, the current results may considerably impact the study of the thermic response of living tissue during laser-based photothermal therapy.

Measuring Turbulent Water Vapor Fluxes Using a Tunable Diode Laser-Based Open-Path Gas Analyzer

The reliable observation and accurate estimates of land–atmosphere water vapor (H2O) flux is essential for ecosystem management and the development of Earth system models. Currently, the most direct measurement method for H2O flux is eddy covariance (EC), which depends on the development of fast-response H2O sensors. In this study, we presented a cost-efficient open-path H2O analyzer (model: HT1800) based on the tunable diode laser absorption spectroscopy (TDLAS) technique, and investigated its applicability for measuring atmospheric turbulent flux of H2O using the EC method. We prepared two HT1800 analyzers with lasers that operate at wavelengths of 1392 nm and 1877 nm, respectively. The field performance of the two analyzers was evaluated through inter-comparative experiments with LI-7500RS and IRGASON, two of the most commonly used H2O analyzers in the EC community. Water vapor densities measured by the three types of analyzers had high overall agreement with the reference sensor; however, they all experienced drift. The mean density drifts of HT1800, LI-7500 and IRGASON were 3.7–5.2%, 4.0% and 3.8%, respectively. Even so, the half-hourly H2O fluxes measured by HT1800 were highly consistent with those by LI-7500RS and IRGASON (with a difference of less than 2%), suggesting that HT1800 can obtain H2O fluxes with high confidence. The HT1800 was also proved to be suitable for EC application in terms of data availability, flux detection limit and response to the high-frequency turbulent variation. Furthermore, we investigated how the spectroscopic effect influences the measurements of H2O density and flux. Despite the fact that the 1392 nm laser was much more susceptible to the spectroscopic effect, the fluxes after correcting for this bias showed excellent agreement with the IRGASON fluxes. Considering the cost advantage in laser and photodetector, the HT1800 analyzer using a 1392 nm infrared laser is a promising and economical solution for EC measurement studies of water vapor.

Analysis of Methods for Measuring Parameters of the Radiation Pattern of Antenna Systems

Measuring the parameters of the antenna pattern is an urgent task in the development and operation of radio engineering systems. This problem can be solved by various methods of antenna measurements. In this case, depending on the radiation zone of the antenna, two main groups of measurement methods are distinguished: methods of direct measurements in the far-field and methods of reconstructive measurements in the near-field. Methods of antenna measurements in the far-field, which allow obtaining direct results, are the most developed and simple, since in the case of the far-field, the angular distribution of the field, regardless of distance, is characterized by a radiation pattern. Methods of the near-field are based on measuring the amplitude-phase distribution of the orthogonal components of the electromagnetic field in the near zone with subsequent recalculation of the parameters and restoration of the spatial radiation pattern of the antenna under study. The comparative analysis of the main groups of antenna measurement methods shows that at the present stage of their development, due to a number of advantages, measurement methods in the near-field with subsequent reconstruction of the radiation pattern of the studied antenna in the far-field are most widely used.

LC-MS/MS methods for direct measurement of sepiapterin and tetrahydrobiopterin in human plasma and clinical applications.

Aim: Tetrahydrobiopterin (BH4), a natural cofactor of aromatic amino acid hydroxylases, and sepiapterin, a natural precursor of BH4, are endogenously present in human plasma. This is the first report on methods for direct quantification of sepiapterin and BH4 in human plasma by LC-MS/MS for pharmacokinetic assessment. Materials & methods: The analytes in plasma were harvested from blood that were treated with 10% ascorbic acid (AA) to a final concentration of 1% AA. Results & conclusion: The quantification methods were validated for calibration ranges of 0.75-500ng/ml and 0.5-500ng/ml for sepiapterin and BH4, respectively. Quantification of analytes was challenging due to their susceptibility to redox reactions. The validated methods were utilized successfully to support clinical development of sepiapterin.