Validity Of Method Research Articles

Advancing Bioanalytical Method Validation: A Comprehensive ICH M10 Approach for Validating LC–MS/MS to Quantify Fluoxetine in Human Plasma and Its Application in Pharmacokinetic Studies

Advancing Bioanalytical Method Validation: A Comprehensive ICH M10 Approach for Validating LC–MS/MS to Quantify Fluoxetine in Human Plasma and Its Application in Pharmacokinetic Studies

A novel fast analytical method for the determination of N-nitroso vonoprazan in vonoprazan tablets and raw materials using LC-ESI-MS/MS

ABSTRACT The presence of N-nitrosamine contaminants in pharmaceuticals, particularly N-nitroso vonoprazan (NVP), poses significant health risks due to their genotoxic and carcinogenic properties. This study describes a novel, rapid analytical method for detecting and quantifying NVP in vonoprazan tablets and raw materials. The NVP was separated and quantified using an LC-ESI-MS/MS system with ESI ionisation and an Exion LC Sciex 5500-QTrap. The system utilised an ACE 3 C18-PFP column with dimensions of 4.6 mm × 150 mm and 3.0 µm. It achieved a high correlation coefficient (R2 = 0.9955) and met linearity and accuracy criteria. The method was developed and validated using ICH guidelines and against standard solutions, and it demonstrated high precision, accuracy, and specificity. The method validation results showed that the quantification is accurate, with an RSD of less than 10% and LOD and LOQ values of 0.5 and 1.0 ng/mL, respectively. The analysis of 150 vonoprazan tablets and 100 raw material samples revealed low levels of NVP, mostly falling below the FDA’s Acceptable Daily Intake limit of 96 ng/day. This novel approach provides a powerful and dependable tool for ensuring the safety and quality of vonoprazan-based pharmaceuticals.

Implementation of machine learning models as a quantitative evaluation tool for preclinical studies in dental education.

Objective, valid, and reliable evaluations are needed in order to develop haptic skills in dental education. The aim of this study is to investigate the validity and reliability of the machine learning method in evaluating the haptic skills of dentistry students. One-hundred fifty 6th semester dental students have performed Class II amalgam (C2A) and composite resin restorations (C2CR), in which all stages were evaluated with Direct Observation Practical Skills forms. The final phase was graded by three trainers and supervisors separately. Standard photographs of the restorations in the final stage were taken from different angles in a special setup and transferred to the Python program which utilized the Structural Similarity algorithm to calculate both the quantitative (numerical) and qualitative (visual) differences of each restoration. The validity and reliability analyses of inter-examiner evaluation were tested by Cronbach's Alpha and Kappa statistics (p=0.05). The intra-examiner reliability between Structural Similarity Index (SSIM) and examiners was found highly reliable in both C2A (α=0.961) and C2CR (α=0.856). The compatibility of final grades given by SSIM (53.07) and examiners (56.85) was statistically insignificant (p>0.05). A significant difference was found between the examiners and SSIM when grading the occlusal surfaces in C2A and on the palatal surfaces of C2CR (p<0.05). The concordance of observer assessments was found almost perfect in C2A (κ=0.806), and acceptable in C2CR (κ=0.769). Although deep machine learning is a promising tool in the evaluation of haptic skills, further improvement and alignments are required for fully objective and reliable validation in all cases of dental training in restorative dentistry.

Mixed material point method formulation, stabilization, and validation for a unified analysis of free-surface and seepage flow

This paper presents a novel stabilized mixed material point method (MPM) designed for the unified modeling of free-surface and seepage flow. The unified formulation integrates the Navier-Stokes equation with the Darcy-Brinkman-Forchheimer equation, effectively capturing flows in both non-porous and porous domains. In contrast to the conventional Eulerian computational fluid dynamics (CFD) solver, which solves the velocity and pressure fields as unknown variables, the proposed method employs a monolithic displacement-pressure formulation adopted from the mixed-form updated-Lagrangian finite element method (FEM). To satisfy the discrete inf-sup stability condition, a stabilization strategy based on the variational multiscale method (VMS) is derived and integrated into the proposed formulation. Another distinctive feature is the implementation of blurred interfaces, which facilitate a seamless and stable transition of flows between free and porous domains, as well as across two distinct porous media. The efficacy of the proposed formulation is verified and validated through several benchmark cases in 1D, 2D, and 3D scenarios. Conducted numerical examples demonstrate enhanced accuracy and stability compared to analytical, experimental, and other numerical solutions.

Stability-indicating RP-HPLC method development and validation for the quantification of amlodipine besylate and valsartan tablets in solid oral dosage form.

The present study discusses the development of simple, rapid, specific, precision, accuracy, stability indicating the HPLC method for the analysis of amlodipine besylate and valsartan tablet dosage form. The chromatographic separation was achieved using phosphate buffer with 1% triethyl amine (pH3.0) as mobile phase-A and mixed Methanol and buffer in the ratio of (65:35)(v/v) as mobile phase-B. The detection of components was made at 237 nm for amlodipine besylate and valsartan. Analytical techniques should enrich sensitivity and specificity for the estimation of pharmaceutical drug products. Evaluated stress studies under different types of ICH conditions. The optimized HPLC method was validated as per the current ICH guidelines. The validated HPLC method was obtained highly specific with linearity ranging between 25 and 200 μgmL-1 of amlodipine besylate and 40-320 μgmL-1 of valsartan and both components correlation coefficient was > 0.999. The method showed high accuracy more than 97%. In stress studies, amlodipine besylate and valsartan were found to be sensitive to acid stress conditions and oxidation stress conditions. The method was found to be suitable for the quality control of amlodipine besylate and valsartan in the tablet as well as in stability-indicating studies. The method was applied to the analysis of stability samples.

Methods established for the detection of mineral levels in whole blood by the dried blood spot technique

Mineral are intimately related to human health and disease, and detection of mineral content in the body is of great significance for the diagnosis and prevention of diseases. In this study, we validated the method developed to detect magnesium (Mg), copper (Cu), iron (Fe), zinc (Zn), and selenium (Se) levels in dried blood spots (DBS). In accordance with the requirements of the guidelines for the Bioanalytical Method Validation Guidance for Industry, we evaluate the linearity, sensitivity, precision, accuracy and selectivity of the developed methods. In addition, Mg, Cu, Fe, Zn and Se were quantified in 195 older adults using DBS technique, and its accuracy was assessed by comparing the results to those detected by inductively coupled plasma-mass spectrometry (ICP-MS). The method has excellent sensitivity and linear range to cover the concentration range of mineral elements in the general population with the required precision, accuracy and selectivity. The correlation coefficients of Mg, Cu, Fe, Zn and Se levels in blood detected by the DBS technique and ICP-MS were 0.638, 0.823, 0.463, 0.728 and 0.751, respectively (all P < 0.05), which indicated that there was a strong correlation between the detection results of the two methods. More than 95 % of the sample results in the Bland-Altman consistency test were within the acceptable limits of agreement (LOA) range, indicating that they had good consistency. DBS technique has good accuracy and reliability in detecting blood mineral levels in the elderly, suggesting potential in the quantification of mineral level in blood.

Assessment of the in vitro metabolic stability of CEP-37440, a selective FAK/ALK inhibitor, in HLMs using fast UPLC–MS/MS method: in silico metabolic lability and DEREK alerts screening

IntroductionCEP-37440 was synthesized and supplied by the research and development division of Teva Branded Pharmaceutical Products (West Chester, PA, United States). CEP-37440 represents a newly developed compound that exhibits selectivity inhibition of Focal Adhesion Kinase and Anaplastic Lymphoma Kinase FAK/ALK receptors, demonstrating novel characteristics as an orally active inhibitor. The simultaneous inhibition of ALK and FAK can effectively address resistance and enhance the therapeutic efficacy against tumors through a synergistic mechanism.MethodsThe objective of this research was to create an LC-MS/MS method that is precise, efficient, environmentally friendly, and possesses a high level of sensitivity for the quantification of CEP-37440 in human liver microsomes (HLMs). The aforementioned approach was subsequently employed to evaluate the metabolic stability of CEP-37440 in HLMs in an in vitro setting. The validation procedures for the LC-MS/MS analytical method in the HLMs were performed following the bio-analytical method validation guidelines set out by the US-FDA. The AGREE program was utilized to assess the ecological impacts of the current LC-MS/MS methodology.Results and DiscussionThe calibration curve linearity was seen in the range of 1–3000 ng/mL. The inter-day accuracy (% RE) exhibited a range of −2.33% to 3.22%, whilst the intra-day accuracy demonstrated a range of −4.33% to 1.39%. The inter-day precision (% RSD) exhibited a range of 0.38% to 3.60%, whilst the intra-day precision demonstrated a range of 0.16% to 6.28%. The determination of the in vitro half-life (t1/2) and moderate intrinsic clearance (Clint) of CEP-37440 yielded values of 23.24 min and 34.74 mL/min/kg, respectively. The current manuscript is considered the first analytical study for CEP-37440 quantification with the application to metabolic stability assessment. These results suggest that CEP-37440 can be categorized as a pharmaceutical agent with a moderate extraction ratio. Consequently, it is postulated that the administration of CEP-37440 to patients may not lead to the accrual of dosages within the human organs. According to in silico P450 metabolic and DEREK software, minor structural alterations to the ethanolamine moiety or substitution of the group in drug design have the potential to enhance the metabolic stability and safety profile of novel derivatives in comparison to CEP-37440.

Validation of An HPLC Method for the Determination of Some Β-Lactams Antibiotics Using A Green Analytical Technique

Green analytical chemistry (GAC) primary goal is to develop environmental and health-friendly analytical methods by reduction or replacement of hazardous substances from analytical procedures. In this research, the application of GAC to quantify five β-lactams antibiotics (cefuroxime sodium, cefaclor, ertapenem sodium, ampicillin sodium and sulbactam sodium) by high-performance liquid chromatography (HPLC) using photodiode arrays (PDA) detector was developed. To achieve this, ethanol was used as a green replacement for methanol and acetonitrile, common solvents in chromatographic procedures. Several chromatographic conditions were investigated to accomplish the optimal conditions. The method validation followed the ICH Q2 (R1) guideline, and the developed method was successfully applied for quantifying some pharmaceutical products.

Experimental validation of an innovative method for minimization of deformation tolerances of reinforced concrete ceilings

AbstractThe static design of reinforced concrete ceilings is mostly based on finite element calculations. If the calculated deformation is too big, a superelevation is carried out in order to optimize the thickness of the ceiling. The superelevation is achieved by setting parts of the formwork a fixed amount higher than the edge areas of the ceilings before concreting. In this contribution, a validation of various numerical methods and a new load approach for the deformation of concrete slabs by means of measurement results is shown whereas the focus is on the multistory support of ceilings, which have not arrived the full Young's modulus.

Stability-indicating high-performance thin-layer chromatography method development and validation for dapagliflozin propanediol monohydrate, vildagliptin, and metformin hydrochloride in active pharmaceutical ingredient and its tablet dosage form

Stability-indicating high-performance thin-layer chromatography method development and validation for dapagliflozin propanediol monohydrate, vildagliptin, and metformin hydrochloride in active pharmaceutical ingredient and its tablet dosage form

Analytical Method Validation and Simultaneous Determination of Ketotifen Fumarate and Cyproheptadine Hydrochloride in Divided Powder by RP-HPLC Method

Ketotifen fumarate and cyproheptadine HCl are the most popular prescription for children at “X” hospital in Yogyakarta. The interest for studying this divided powder was related to the stability test towards human health. Hence, it was important to developed a validated analytical method to quantify content of active drug from sample. In this study, a reversed phase HPLC (RP-HPLC) method was validated and applied for determining content of ketotifen fumarate and cyproheptadine hydrochloride in divided powder. The developed RP-HPLC method was met the requirement of selectivity and sensitivity. Calibration curve formulas of ketotifen fumarate and cyproheptadine hydrochloride were y = 27714x-79111 (r=0.9945) and y = 26324x+72581 (r=0.9935) in the range of 10.9-54.5 and 10.6-53.0 µg/mL, respectively. Accuracy and intermediate precision were assessed on both standard solution and samples spiked with standard solution of ketotifen fumarate and cyproheptadine hydrochloride. It was found that both standard solution and the spiked samples solution were met the requirement of recovery of 80-110% and RSD of less than 7.3% for intraday and interday analysis. Content of ketotifen fumarate and cyproheptadine hydrochloride in sample (n=7) were 16.574±0.098 and 30.640±0.035 µg/mL, respectively. It can be concluded that the RP-HPLC method was successfully validated and applied in the determination of ketotifen fumarate and cyproheptadine hydrochloride in divided powder.

Physiological definition for region of interest selection in electrical impedance tomography data: description and validation of a novel method.

&#xD;Geometrical region of interest (ROI) selection in electrical impedance tomography (EIT) monitoring may lack sensitivity to subtle changes in ventilation distribution. Therefore, we demonstrate a new physiological method for ROI definition. This is relevant when using ROIs to compute subsequent EIT-parameters, such as the ventral-to-dorsal ratio during a positive end-expiratory pressure (PEEP) trial. &#xD;&#xD;Approach:&#xD;Our physiological approach divides an EIT image to ensure exactly 50% tidal impedance variation in the ventral and dorsal region. To demonstrate the effects of our new method, EIT measurements during a decremental PEEP trial in 49 mechanically ventilated ICU-patients were used. We compared the center of ventilation (CoV), a robust parameter for changes in ventro-dorsal ventilation distribution, to our physiological ROI selection method and different commonly used ROI selection methods. Moreover, we determined the impact of different ROI selection methods on the PEEP level corresponding to a ventral-to-dorsal ratio closest to 1.&#xD;&#xD;Main results:&#xD;The division line separating the ventral and dorsal ROI was closer to the CoV for our new physiological method for ROI selection compared to geometrical ROI definition. Moreover, the PEEP level corresponding to a ventral-to-dorsal ratio of 1 is strongly influenced by the chosen ROI selection method, which could have a profound clinical impact; the within-subject range of PEEP level was 6.2 cmH2O depending on the chosen ROI selection method.&#xD;&#xD;Significance:&#xD;Our novel physiological method for ROI definition is sensitive to subtle ventilation-induced changes in regional impedance (i.e. due to (de)recruitment) during mechanical ventilation, similar to the CoV. &#xD;&#xD.

Development of Reduced-Order-Discrete-Module method for hydroelastic analysis of floating flexible structures

The present study proposes a novel method for analyzing the hydroelastic response of floating flexible structures based on Reduced-Order-Discrete-Module (RODM) model. In this model, the floating flexible structure is discretized into a finite number of modules. The hydrodynamic problem is simplified as the interaction between waves and multiple modules. The hydroelastic response is approximated by solving the motion equation of the multibody system, in which the mass and stiffness of the structure are obtained from the reduced-order matrices by the finite element method with a system equivalent reduction expansion process. By using the transformation matrix, the detailed floating structure response can be reconstructed from the multibody dynamics. The validity of the proposed method was demonstrated by comparing the results with the experimental data and other existing methods. The results show that this study has developed an accurate hydroelastic model to analyze the hydroelastic response of floating flexible structures. A module number selection formula is proposed to select the appropriate number of modules based on the exciting force frequency. This model is relatively easy to implement for the hydroelastic problem of interconnection modules and take into account the spatial inhomogeneity of wind/wave field. The proposed model can offer a useful tool for analyzing the hydroelastic response of the offshore floating photovoltaic systems.

Cross validation of pharmacokinetic bioanalytical methods: Experimental and statistical design

Pharmacokinetic (PK) analysis is an integral part of drug development. Health agency guidance provides development and validation recommendations for PK bioanalytical methods run in one laboratory. However, as a drug development program progresses, a PK bioanalytical method may need to be run in more than one laboratory. Additionally, a PK bioanalytical method format may change and a new method platform may be validated and implemented during the drug development cycle. Here we describe the cross validation strategy for comparisons of two validated bioanalytical methods used to generate PK data within the same study or across different studies. Current guidance for cross validations is limited and, therefore, Genentech, Inc. has developed a cross validation experimental strategy that utilizes incurred samples along with a comprehensive statistical analysis. One hundred incurred study samples over the applicable range of concentrations are selected based on four quartiles (Q) of in-study concentration levels. The samples are assayed once in the two bioanalytical methods. Bioanalytical method equivalency is assessed for the 100 samples based on pre-specified acceptability criterion: the two methods are considered equivalent if the percent differences in the lower and upper bound limits of the 90 % confidence interval (CI) are both within ±30 %. Quartile by concentration analysis using the same criterion may also need to be performed. A Bland-Altman plot of the percent difference of sample concentrations versus the mean concentration of each sample is also created to help further characterize the data. This strategy is a robust assessment of PK bioanalytical method equivalency and includes subgroup analyses by concentration to assess for biases. This strategy was implemented in two case studies: 1) two different laboratories using the same bioanalytical method and 2) a bioanalytical method platform change from enzyme-linked immunosorbent assay (ELISA) to multiplexing immunoaffinity (IA) liquid chromatography tandem mass spectrometry (IA LC-MS/MS).

Development and Validation of a Novel Method Using QuEChERS and UHPLC-MS-MS for the Determination of Multiple Emerging Fungicides in Surface Waters

The increasing global reliance on pesticides for agricultural pest control has raised significant environmental concerns, particularly due to inadequate monitoring of emerging chemicals in surface waters. This study addresses the potential contamination of aquatic ecosystems by developing and validating a method for detecting trace amounts of four recently registered fungicides: three succinate dehydrogenase inhibitors (fluopyram, penthiopyrad, pydiflumetofen) and fluopicolide, a structurally related fungicide. Employing QuEChERS-based sample extraction combined with ultra-high-performance liquid chromatography (UHPLC-MS-MS), this method achieves detection limits of 0.1 to 0.2 μg/L, with recovery rates between 90% and 110%, and intra-day relative standard deviation values well within the acceptable range of less than 20%. Applied to surface grab water samples from the greater Melbourne area, Australia, the method successfully identified all four fungicides at trace levels, including a notable high concentration of fluopyram (7.3 μg/L) during autumn, with the others intermittently detected at lower concentrations. This study represents the first documented instance of quantifiable detections of these four fungicides in Australian surface water systems. Given their high toxicity to several organisms and the limited global data on these substances, our findings underscore the critical need for continuous monitoring to inform strategies to safeguard aquatic ecosystems from these chemicals.

Development and Design Validation of an Inflow-Settling Chamber for Turbomachinery Test-Benches

At Leibniz University of Hannover, Germany, a new turbomachinery test facility has been built over the last few years. A major part of this facility is a new 6 MW compressor station, which is connected to a large piping system, both designed and built by AERZEN. This system provides air supply to several wind tunnel and turbomachinery test rigs, e.g., axial turbines and axial compressors. These test rigs are designed to conduct high-quality aerodynamic, aeroelastic, and aeroacoustic measurements to increase physical understanding of steady and unsteady effects in turbomachines. One primary purpose of these investigations is the validation of aerodynamic and aeroacoustic numerical methods. To provide precise boundary conditions for the validation process, extremely high homogeneity of the inflow to the investigated experimental setup is imminent. Thus, customized settling chambers have been developed using analytical and numerical design methods. The authors have chosen to follow basic aerodynamic design steps, using analytical assumptions for the inlet section, the “mixing” area of a settling chamber, and the outlet nozzle in combination with state-of-the-art numerical investigations. In early 2020, the first settling chamber was brought into operation for the acceptance tests. In order to collect high-resolution flow field data during the tests, Leibniz University and AERZEN have designed a unique measurement device for robust and fast in-line flow field measurements. For this measurement device, total pressure and total-temperature rake probes, as well as traversing multi-hole probes, have been used in combination to receive high-resolution flow field data at the outlet section of the settling chamber. The paper provides information about the design process of the settling chamber, the developed measurement device, and measurement data gained from the acceptance tests.

Pseudo Master Curve Analysis of an Infinite Number of Parallel First-Order Reactions: Improved Distributed Activation Energy Model.

The so-called Distributed Activation Energy Model (DAEM) has been used extensively, mainly to analyze pyrolysis reactions of solid reactants. The model expresses many parallel first-order reactions using the distributions of activation energy f(E) and frequency factor k 0(E). Miura and Maki presented a method to estimate both f(E) and k 0(E) in the DAEM in 1998. This model has been used successfully by many researchers. In this paper more general basic equations are derived for describing an infinite number of parallel first-order reactions by extending the basic equations for the finite number of parallel first-order reactions. Revisiting the Miura-Maki method based on the general basic equations, a graphical analysis method that may be called "Pseudo Master Curve Analysis" is presented. The method not only supplements the Miura-Maki method but gives the underlying concept of the Miura-Maki method clearly. It is also shown that the graphical method can be applicable to analyze single reactions and the experimental data obtained using isothermal reaction techniques. Next, a method that improves the estimation accuracy of k 0(E) is presented. Practical examples analyzing several experimental data are also given to show the usefulness and validity of the Miura-Maki method and the graphical method. Through the examination, it is proposed that the DAEM should be renamed, for example, as the Distributed Rate Constant Model (DRCM).

Assessing Biofilm at the Bedside: Exploring Reliable Accessible Biofilm Detection Methods

Introduction: Biofilm is linked through a variety of mechanisms to the pathogenesis of chronic wounds. However, accurate biofilm detection is challenging, demanding highly specialized and technically complex methods rendering it unapplicable for most clinical settings. This study evaluated promising methods of bedside biofilm localization, fluorescence imaging of wound bacterial loads, and biofilm blotting by comparing their performance against validation scanning electron microscopy (SEM). Methods: In this clinical trial, 40 chronic hard-to-heal wounds underwent the following assessments: (1) clinical signs of biofilm (CSB), (2) biofilm blotting, (3) fluorescence imaging for localizing bacterial loads, wound scraping taken for (4) SEM to confirm matrix encased bacteria (biofilm), and (5) PCR (Polymerase Chain Reaction) and NGS (Next Generation Sequencing) to determine absolute bacterial load and species present. We used a combination of SEM and PCR microbiology to calculate the diagnostic accuracy measures of the CSB, biofilm blotting assay, and fluorescence imaging. Results: Study data demonstrate that 62.5% of wounds were identified as biofilm-positive based on SEM and microbiological assessment. By employing this method to determine the gold truth, and thus calculate accuracy measures for all methods, fluorescence imaging demonstrated superior sensitivity (84%) and accuracy (63%) compared to CSB (sensitivity 44% and accuracy 43%) and biofilm blotting (sensitivity 24% and accuracy 40%). Biofilm blotting exhibited the highest specificity (64%), albeit with lower sensitivity and accuracy. Using SEM alone as the validation method slightly altered the results, but all trends held constant. Discussion: This trial provides the first comparative assessment of bedside methods for wound biofilm detection. We report the diagnostic accuracy measures of these more feasibly implementable methods versus laboratory-based SEM. Fluorescence imaging showed the greatest number of true positives (highest sensitivity), which is clinically relevant and provides assurance that no pathogenic bacteria will be missed. It effectively alerted regions of biofilm at the point-of-care with greater accuracy than standard clinical assessment (CSB) or biofilm blotting paper, providing actionable information that will likely translate into enhanced therapeutic approaches and better patient outcomes.

Dysmenorrhea and Its Impact on Patients’ Quality of Life—A Cross-Sectional Study

Background: Dysmenorrhea is a common condition that may have negative effects on social life, couples’ relationships and professional activities. The objectives of this study were to evaluate the prevalence, risk factors and characteristics of dysmenorrhea and its impact on patients’ quality of life using a specific self-questionnaire named “DysmenQoL questionnaire”. We also checked the validity and reliability of this questionnaire in our population. Methods: We conducted a cross-sectional study that included 504 participants of reproductive age between 18 and 45 years of age. The data were collected with an original form divided into three sections. The last section (DysmenQoL questionnaire) included 20 statements scored from 1 (“never”) to 5 (“every time”) that evaluates the effects of menstrual pain on health and feelings, daily activities, relationships and professional activity. We calculated the sum of the scores for each statement and we called it the “DysmenQoL score”. Results: The prevalence of dysmenorrhea was 83.7%. The presence of dysmenorrhea was statistically significant associated with the degree of menstrual bleeding (p = 0.017), the presence of infertility (p = 0.034) and dyspareunia (p = 0.002), but also with the presence of premenstrual syndrome and a family history of dysmenorrhea (p &lt; 0.001). Among the participants with dysmenorrhea, 73.9% considered that this symptom affected their quality of life, and this was correlated with pain intensity and the DysmenQoL score (p &lt; 0.001). A significant difference regarding the DysmenQoL score depending on the pain intensity, frequency and duration of dysmenorrhea and the methods used to reduce the pain was observed. Conclusions: Dysmenorrhea had a high prevalence among the participants included in the study, and its presence was associated with a series of risk factors. Most women considered that dysmenorrhea affected their quality of life. The DysmenQoL questionnaire proved to be a reliable and valid method for evaluating the impact of dysmenorrhea on quality of life.

Developing and validating an L2 writing willingness to communicate scale: A sequential embedded mixed-methods approach

Current willingness to communicate (WTC) scales center on WTC in general second language (L2) learning, while L2 writing WTC is underrepresented. This study intended to close this gap by developing and validating an L2 writing WTC scale. A three-phase sequential embedded mixed-methods design was adopted to overcome the over-reliance on quantitative data and provide adequate evidence of validity. Nineteen items were generated based on our literature search and thematic analysis of the interview data ( n = 10). With quantitative data collected from 288 learners of English as a foreign language (EFL), the psychometric properties of the initial scale were examined by exploratory factor analysis. After that, the revised 17-item questionnaire was validated by confirmatory factor analysis and other validation methods with data from 224 EFL learners. The results indicated that the underlying structure involved writing task traits, English language ideology, writing teacher support, interest in English language, and self-perception of English language proficiency. The scale was further validated through factor analysis of the quantitative data ( n = 173) and thematic analysis of the immediate retrospective interview data ( n = 12) from EFL learners to test its generalizability in other L2 learning contexts and for face validity evidence. The findings showcased a promising mixed-methods design for scale development and clarified the underlying factors of L2 writing WTC. Implications for scale development and the teaching and learning of L2 writing were discussed.