Fully Automated Valve Segmentation for Blood Flow Assessment From 4D Flow MRI Including Automated Cardiac Valve Tracking and Transvalvular Velocity Mapping.

BACKGROUND: Automated 4D flow MRI valvular flow quantification without time-consuming manual segmentation might improve workflow. PURPOSE: Compare automated valve segmentation (AS) to manual (MS), and manually corrected automated segmentation (AMS), in corrected atrioventricular septum defect (c-AVSD) patients and healthy volunteers, for assessing net forward volume (NFV) and regurgitation fraction (RF). STUDY TYPE: Retrospective. POPULATION: 27 c-AVSD patients (median, 23 years; interquartile range, 16-31 years) and 24 healthy volunteers (25 years; 12.5-36.5 years). FIELD STRENGTH/SEQUENCE: Whole-heart 4D flow MRI and cine steady-state free precession at 3T. ASSESSMENT: After automatic valve tracking, valve annuli were segmented on time-resolved reformatted trans-valvular velocity images by AS, MS, and AMS. NFV was calculated for all valves, and RF for right and left atrioventricular valves (RAVV and LAVV). NFV variation (standard deviation divided by mean NFV) and NFV differences (NFV difference of a valve vs. mean NFV of other valves) expressed internal NFV consistency. STATISTICAL TESTS: Comparisons between methods were assessed by Wilcoxon signed-rank tests, and intra/interobserver variability by intraclass correlation coefficients (ICCs). P < 0.05 was considered statistically significant, with multiple testing correction. RESULTS: AMS mean analysis time was significantly shorter compared with MS (5.3 ± 1.6 minutes vs. 9.1 ± 2.5 minutes). MS NFV variation (6.0%) was significantly smaller compared with AMS (6.3%), and AS (8.2%). Median NFV difference of RAVV, LAVV, PV, and AoV between segmentation methods ranged from -0.7-1.0 mL, -0.5-2.8 mL, -1.1-3.6 mL, and - 3.1--2.1 mL, respectively. Median RAVV and LAVV RF, between 7.1%-7.5% and 3.8%-4.3%, respectively, were not significantly different between methods. Intraobserver/interobserver agreement for AMS and MS was strong-to-excellent for NFV and RF (ICC ≥0.88). DATA CONCLUSION: MS demonstrates strongest internal consistency, followed closely by AMS, and AS. Automated segmentation, with or without manual correction, can be considered for 4D flow MRI valvular flow quantification. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 3.

Application of Time-Scale Decomposition of Entropy for Eye Movement Analysis.

The methods for nonlinear time series analysis were used in the presented research to reveal eye movement signal characteristics. Three measures were used: approximate entropy, fuzzy entropy, and the Largest Lyapunov Exponent, for which the multilevel maps (MMs), being their time-scale decomposition, were defined. To check whether the estimated characteristics might be useful in eye movement events detection, these structures were applied in the classification process conducted with the usage of the kNN method. The elements of three MMs were used to define feature vectors for this process. They consisted of differently combined MM segments, belonging either to one or several selected levels, as well as included values either of one or all the analysed measures. Such a classification produced an improvement in the accuracy for saccadic latency and saccade, when compared with the previously conducted studies using eye movement dynamics.

Evosep One Enables Robust Deep Proteome Coverage Using Tandem Mass Tags while Significantly Reducing Instrument Time.

The balance between comprehensively analyzing the proteome and using valuable mass spectrometry time is a genuine challenge in the field of proteomics. Multidimensional fractionation strategies have significantly increased proteome coverage, but often at the cost of increased mass analysis time, despite advances in mass spectrometer acquisition rates. Recently, the Evosep One liquid chromatography system was shown to analyze peptide samples in a high-throughput manner without sacrificing in-depth proteomics coverage. We demonstrate the incorporation of Evosep One technology into our multiplexing workflow for analysis of tandem mass tag (TMT)-labeled nonsmall cell lung carcinoma (NSCLC) patient-derived xenografts (PDXs). By the use of a 30 samples per day Evosep workflow, >12 000 proteins were identified in 48 h of mass spectrometry time, which is comparable to the number of proteins identified by our conventional concatenated EASY-nLC workflow in 60 h. Shorter Evosep gradient lengths reduced the number of protein identifications by 10% while decreasing the mass analysis time by 50%. This Evosep workflow will enable quantitative analysis of multiplexed samples in less time without conceding depth of proteome coverage.

Single-run capillary electrophoresis method for the fast simultaneous determination of amoxicillin, clavulanate, and potassium.

We report a new fast method for the simultaneous determination of amoxicillin, clavulanate, and potassium by capillary electrophoresis with capacitively coupled contactless conductivity detection. Samples containing potassium as the cation, and both amoxicillin and clavulanate as anions were determined simultaneously in a single run (in less than 45 s) using 10 mmol/L of both 2-amino-2-hydroxymethyl-propane-1,3-diol and 3-{[2-hydroxy-1,1-bis(hydroxymethyl)ethyl]amino}-1-propanesulfonic acid (pH 8.4) as the background electrolyte. Limits of detection were 25.0, 5.0, and 4.0 µmol/L for amoxicillin, clavulanate, and potassium, respectively. The proposed method is inexpensive, simple, fast (75 injections h-1 ), environment friendly (minimal waste generation), and accurate (recovery values between 98 and 103%). The results obtained with the proposed method were statistically similar (95% confidence level) to those obtained by using high-performance liquid chromatography (amoxicillin and clavulanate) and flame photometry (potassium).

Predicting analysis time in events-driven clinical trials using accumulating time-to-event surrogate information.

For clinical trials with time-to-event endpoints, predicting the accrual of the events of interest with precision is critical in determining the timing of interim and final analyses. For example, overall survival (OS) is often chosen as the primary efficacy endpoint in oncology studies, with planned interim and final analyses at a pre-specified number of deaths. Often, correlated surrogate information, such as time-to-progression (TTP) and progression-free survival, are also collected as secondary efficacy endpoints. It would be appealing to borrow strength from the surrogate information to improve the precision of the analysis time prediction. Currently available methods in the literature for predicting analysis timings do not consider utilizing the surrogate information. In this article, using OS and TTP as an example, a general parametric model for OS and TTP is proposed, with the assumption that disease progression could change the course of the overall survival. Progression-free survival, related both to OS and TTP, will be handled separately, as it can be derived from OS and TTP. The authors seek to develop a prediction procedure using a Bayesian method and provide detailed implementation strategies under certain assumptions. Simulations are performed to evaluate the performance of the proposed method. An application to a real study is also provided. Copyright © 2015 John Wiley & Sons, Ltd.

An evaluation of isocentre shift magnitude and treatment site on image-guided radiation therapy online decision analysis times.

INTRODUCTION: The ability to capture more anatomical detail in cone-beam computed tomography (CBCT) imaging compared to kilovoltage (kV) and megavoltage (MV) imaging, has seen a documented shift towards CBCT image verification and staff adopting more extensive image analysis processes. The timeframe associated with assessing online CBCT images, termed the online decision analysis time, if drawn out, can affect treatment efficiency and accuracy. This study aimed to determine the current CBCT online decision analysis time at Radiation Oncology Princess Alexandra Ipswich Road (ROPAIR) and investigate the influence of isocentre shift magnitude and treatment site considerations on this timeframe. METHODS: This retrospective clinical audit collected treatment parameters from 202 CBCT images over 2 treatment days. The online decision analysis time was calculated by subtracting the image acquisition timestamp from the image verification shift application timestamp. The quantitative data were analysed using mean, standard deviation, and range in the following categories: all CBCTs, CBCTs grouped by isocentre shift magnitude and CBCTs grouped by treatment site. Content analysis was performed on staff comments made during image analysis. RESULTS: The average online decision analysis time was 2:37 ± 1:28 min. On average approximately, head and neck, spine and extremity treatment sites measured 1 min, pelvis, breast, and chest measured 2-3 min with abdomen measuring 4 min. Common categories reported in staff comments included anatomical changes, repositioning, and organs at risk size. CONCLUSION: The results provide baseline online decision analysis times. Further refinement is required to determine if the image match method, treatment site considerations, and rotational discrepancies influence this timeframe.

Performance testing of four automated coagulation analyzers in a university hospital setting with focus on global coagulation assays.

INTRODUCTION: Several automated coagulation analyzers are available for laboratory use. In a university hospital central laboratory, we compared four different instruments. The results for global coagulation assays are presented here. METHODS: ACL TOP 750 CTS (Instrumentation Laboratory), Atellica COAG 360 (COAG 360), BCS XP (both Siemens Healthineers), and cobas t 711 (Roche Diagnostics) were compared. For inter-instrument comparison, five basic coagulation parameters were analyzed in 476 patient plasma samples. Additional assessments included precision testing using commercial control samples and plasma pools, analysis time for a defined set of samples, sample capacity testing, minimum required sample volumes, and detection quality for hemolytic, icteric, or lipemic (HIL) interferences. RESULTS: Good concordance between different instruments was evident from Bland-Altman plots and comparison of data from each instrument with the overall median (τ≥0.8). Shortest analysis times were found for BCS XP and COAG 360, COAG 360 revealed highest sample capacity. Observed required sample volumes were broadly in line with manufacturer specifications and varied according to instrument configurations. HIL detection differed between instruments and was best with ACL TOP 750 CTS. CONCLUSION: The four analyzers showed similarly high levels of concordance, although some variations were apparent. The most significant differences between the instruments were found in analysis times and sample capacity. Analyzer capabilities must be considered when selecting laboratory equipment and defining algorithms for clinical practice.

Impact of particle size gradients on the apparent efficiency of chromatographic columns.

In this paper, the benefits of using columns packed with particles of decreasing size (particle size gradient) in liquid chromatography was investigated from a theoretical point of view. It is indeed well known that such columns may be useful in gradient elution, since the decrease of particle size along the chromatographic column can provide extra peak focusing effect. In the present contribution, several parameters (i.e., mobile phase gradient steepness, retention times and operating pressures) were considered and the kinetic performance of various types of columns packed with particle size gradient were evaluated. In the best case, about 15-20% gain in efficiency can be expected at a given retention time when utilizing a particle size gradient, compared to constant particle size. Conversely, when fixing efficiency, the analysis time can be decreased by about 15% with an optimal particle size gradient. However, it is also important to keep in mind that a too large a particle size gradient can result in lower efficiencies than a column packed with monodisperse packing. We have introduced the gd value, which is a dimensionless measure of the particle size gradient steepness that measures the relative variation of particle diameter throughout the column with respect to the average. We finally observed that gd=0.3-0.4 provides the highest gain under practically useful conditions.

On the performance of conically shaped columns: Theory and practice.

The chromatographic performance (speed, efficiency, and gradient peak capacity for the same analysis time) of conical columns are investigated from fundamental and experimental viewpoints. A stainless steel, conically shaped column (2.1 mm i.d/4.2 mm i.d. × 15 cm long, 0.4° opening angle) was prepared in-house and packed with 5 µm XBridge-C18 fully porous particles. Its performance was compared to that of a conventional 3.0 mm × 15 cm cylindrical column packed with the same batch of particles. Both Giddings' theory of non-uniform columns and experiments agree and show that, irrespective of flow direction, the conical column is 15% less efficient than the conventional column. Remarkably, Blumberg's theory of band broadening in gradient elution mode predicts that conical columns may outperform conventional cylindrical columns if the ratio of their outlet i.d. to their inlet i.d. is 0.95 and 0.80 for small molecule and peptide mixtures, respectively. The maximum relative gain is marginal as it does not exceed a few percents. The theory reveals that the flow direction should be from the wide to the narrow end of the conical column in order to deliver the highest peak capacity. In agreement with the theory, the observed losses in absolute peak capacity for the same analysis time are 14.5% (narrow to wide end) and only 11.0% (wide to the narrow end) for small molecules (n-alkanophenones). They are 14.2% (narrow to wide end) and only 8.5% (wide to the narrow end) for peptide samples (bombesin). Additionally, conical columns reduce peak tailing with respect to standard columns. They are suitable column technology for ultra-fast gradient separations as they also minimize sample dispersion through the narrow i.d. outlet frit.

Assessing the effects of different prebiotic dietary oligosaccharides in sheep milk ice cream.

The objective of this study was to assess the effects of different prebiotic dietary oligosaccharides (inulin, fructo-oligosaccharide, galacto-oligossacaride, short-chain fructo-oligosaccharide, resistant starch, corn dietary oligosaccharide and polydextrose) in non-fat sheep milk ice cream processing through physical parameters, water mobility and thermal analysis. Overall, the fat replacement by dietary prebiotic oligosaccharides significantly decreased the melting time, melting temperature and the fraction and relaxation time for fat and bound water (T22) while increased the white intensity and glass transition temperature. The replacement of sheep milk fat by prebiotics in sheep milk ice cream constitutes an interesting option to enhance nutritional aspects and develop a functional food.

Achievable separation performance and analysis time in current liquid chromatographic practice for monoclonal antibody separations.

The separation performance of a chromatographic system is often described in terms of column efficiency and peak capacity. Thanks to the new developments in column technology over the past few years, the achievable peak capacity drastically improved and the analysis time can be significantly shortened. Indeed, highly efficient wide-pore reversed-phase (RPLC) materials packed with small fully porous and superficially porous particles can be successfully used for the analytical characterization of therapeutic proteins. For non denaturating chromatographic approaches, such as ion exchange (IEX) and size-exclusion chromatography (SEC), non-porous ion-exchanger as well as sub -3µm size exclusion supports are commercially available and open new avenues in protein separations. In this study, the current possibilities offered by chromatography for the characterization of monoclonal antibody (mAb) are discussed. For this purpose, recently published data have been reviewed and calculations were performed to compare the maximum achievable peak capacity and related analysis times using typical samples under RPLC, IEX and SEC conditions. Carefully chosen realistic column pressure, mobile phase temperature, flow rate and column dimensions were considered for the case studies discussed through the paper.

Horizontal Long Axis Imaging Plane for Evaluation of Right Ventricular Function on Cardiac Magnetic Resonance Imaging.

PURPOSE: The purpose of this study was to evaluate a horizontal long axis (HLA) magnetic resonance imaging (MRI) plane aligned to the long axis of the right ventricular (RV) cavity for functional analysis by comparing the measurement variability and time required for the analysis with that using a short-axis (SAX) image orientation. MATERIALS AND METHODS: Thirty-four cardiac MRI exams with cine balanced steady-state free precession image stacks in both the SAX and the HLA of the RV (RHLA) were evaluated. Two reviewers independently traced RV endocardial borders on each image of the cine stacks. The time required to complete each set of traces was recorded, and the RV end-diastolic volume, end-systolic volume, and ejection fraction were calculated. Analysis times and RV measurements were compared between the two orientations. RESULTS: Analysis time for each reviewer was significantly shorter for the RHLA stack (reviewer 1 = 6.4 ± 1.8 min, reviewer 2 = 6.0 ± 3.3 min) than for the SAX stack (7.5 ± 2.1 and 6.9 ± 3.6 min, respectively; P < 0.002). Bland-Altman analysis revealed lower mean differences, limits of agreement, and coefficients of variation for RV measurements obtained with the RHLA stack. CONCLUSIONS: RV functional analysis using a RHLA stack resulted in shorter analysis times and lower measurement variability than for a SAX stack orientation.

Development, optimization, validation and application of faster gas chromatography - flame ionization detector method for the analysis of total petroleum hydrocarbons in contaminated soils.

This paper presents an important new approach to improving the timeliness of Total Petroleum Hydrocarbon (TPH) analysis in the soil by Gas Chromatography - Flame Ionization Detector (GC-FID) using the CCME Canada-Wide Standard reference method. The Canada-Wide Standard (CWS) method is used for the analysis of petroleum hydrocarbon compounds across Canada. However, inter-laboratory application of this method for the analysis of TPH in the soil has often shown considerable variability in the results. This could be due, in part, to the different gas chromatography (GC) conditions, other steps involved in the method, as well as the soil properties. In addition, there are differences in the interpretation of the GC results, which impacts the determination of the effectiveness of remediation at hydrocarbon-contaminated sites. In this work, multivariate experimental design approach was used to develop and validate the analytical method for a faster quantitative analysis of TPH in (contaminated) soil. A fractional factorial design (fFD) was used to screen six factors to identify the most significant factors impacting the analysis. These factors included: injection volume (µL), injection temperature (°C), oven program (°C/min), detector temperature (°C), carrier gas flow rate (mL/min) and solvent ratio (v/v hexane/dichloromethane). The most important factors (carrier gas flow rate and oven program) were then optimized using a central composite response surface design. Robustness testing and validation of model compares favourably with the experimental results with percentage difference of 2.78% for the analysis time. This research successfully reduced the method's standard analytical time from 20 to 8min with all the carbon fractions eluting. The method was successfully applied for fast TPH analysis of Bunker C oil contaminated soil. A reduced analytical time would offer many benefits including an improved laboratory reporting times, and overall improved clean up efficiency. The method was successfully applied for the analysis of TPH of Bunker C oil in contaminated soil.

A critical overview of non-aqueous capillary electrophoresis. Part II: separation efficiency and analysis time.

A survey of the literature on non-aqueous capillary zone electrophoresis leaves one with the impression of a prevailing notion that non-aqueous conditions are principally more favorable than conventional aqueous media. Specifically, the application of organic solvents in capillary zone electrophoresis (CZE) is believed to provide the general advantages of superior separation efficiency, higher applicable electric field strength, and shorter analysis time. These advantages, however, are often claimed without providing any experimental evidence, or based on rather uncritical comparisons of limited sets of arbitrarily selected separation results. Therefore, the performance characteristics of non-aqueous vs. aqueous CZE certainly deserve closer scrutiny. The primary intention of Part II of this review is to give a critical survey of the literature on non-aqueous capillary electrophoresis (NACE) that has emerged over the last five years. Emphasis is mainly placed on those studies that are concerned with the aspects of plate height, plate number, and the crucial mechanisms contributing to zone broadening, both in organic and aqueous conditions. To facilitate a deeper understanding, this treatment covers also the theoretical fundamentals of peak dispersion phenomena arising from wall adsorption; concentration overload (electromigration dispersion); longitudinal diffusion; and thermal gradients. Theoretically achievable plate numbers are discussed, both under limiting (at zero ionic strength) and application-relevant conditions (at finite ionic strength). In addition, the impact of the superimposed electroosmotic flow contributions to overall CZE performance is addressed, both for aqueous and non-aqueous media. It was concluded that for peak dispersion due to wall adsorption and due to concentration overload (electromigration dispersion, leading to peak triangulation) no general conjunction with the solvent can be deduced. This is in contrast to longitudinal diffusion: the plate height (and the plate number) obtainable under limiting conditions (at zero ionic strength) has the same ultimate value for all solvents. However, in background electrolytes with finite ionic strength, the maximum reachable plate number depends on the solvent, and in water it is higher than in the most commonly used organic solvents: methanol and acetonitrile. Thermal peak broadening is also larger in the organic solvents if compared to aqueous solutions under comparable conditions. However, its influence on the plate height is negligible under conditions established with commercial instrumentation. From the laws of electric and thermal conductance, it follows that no general conclusion can be drawn that with organic solvents higher field strength can be applied and shorter analysis time can be reached; the contrary is more evident: under comparable conditions aqueous solutions lead to more favorable results. This comprehensive analysis provides strong evidence that the broadly held notion of non-aqueous CZE being principally superior to aqueous CZE is a myth rather than a fact. However, several studies in which the employment of non-aqueous conditions has been instrumental to solve challenging analytical problems demonstrate that the intelligent use of non-aqueous CE has and will continue having its place in modern separation science.

Laboratory turnaround times in response to an abrupt increase in specimen testing after a natural disaster.

OBJECTIVES: Understanding how key indicators change during extreme circumstances could help laboratories maintain high standards when responding to disasters. We assessed the effects of an earthquake on turnaround times (TATs) at a hospital laboratory. METHODS: We examined TATs for 709,786 potassium tests and 196,795 urine cultures from February 2010 to January 2013. Hospital and community data were evaluated separately and compared during the transport, registration (accessioning), and analysis time phases. RESULTS: After the earthquake, the laboratory undertook approximately 70% of the nonacute community specimen testing. Initially, community transport times increased by 20 to 27 hours and remained 2 to 3 hours above prequake levels. Registration time increased by 10 to 20 minutes (hospital) and 30 to 45 minutes (community) for a short period. During the initial few months, community urine culture analysis time increased by more than 50 hours. CONCLUSIONS: The increase in specimen numbers affected short- and long-duration test TATs differently. Streamlining and automating processes reduced registration and analysis times. Increased transport time was outside the control of the laboratory.

Artroplastias de quadril no Sistema Único de Saúde: análise dos dados brasileiros de 2008 a 2015 / Hip replacements in the Brazilian Unified Health System: review of national data from 2008 to 2015

Objetivo: Analisar a incidência, distribuição espacial e os fatores que influenciam a realização de artroplastias de quadril no SUS, especialmente artroplastias totais (ATQs). Material e Método: Estudo ecológico analítico nível III, analisou uma série temporal e a distribuição espacial dos casos de artroplastias de quadril realizadas no SUS entre 2008 e 2015, através de dados obtidos da plataforma DATASUS. Resultados: Foram realizadas 166.365 artroplastias de quadril, sendo 94.737 (56,9%) ATQs primárias. O custo total foi R$636.332.731,90. Houve aumento no número de cirurgias realizadas, em especial após 2012. A média anual de ATQ primárias foi 11.842,1 cirurgias/ano (dp=868,3 cirurgias/ano), a um custo médio de R$45.473.445,65/ano (dp=R$8.269.970,1/ano). Em 2012 as não-cimentadas e híbridas se tornaram as mais comuns. A distribuição das frequencias nos estados brasileiros é heterogênea e os fatores associados foram proporção de indivíduos com mais de 50 anos de idade (p=0,000175) e proporção de municípios com IDH alto ou muito alto (p=0,037). Conclusão: A incidência de ATQs no SUS aumentou no período de 2008 a 2015. Sua distribuição foi maior nos Estados com maior proporção de indivíduos >50 anos e com maior proporção de municípios com IDH alto ou muito alto. A incidência de ATQs primárias cimentadas foi superada pelas não cimentadas e híbridas em 2012.

Objective: To evaluate the incidence, spatial distribution and the factors that influence the numbers of hip arthroplasties in the Unified Health System in Brazil(SUS), especially total hip arthroplasties (THA). Methods: An level III analytical ecological study of the time series and the spatial distribution of the cases of hip arthroplasties performed in SUS between 2008 and 2015, using of data obtained from the DATASUS platform. Results: 166,365 hip arthroplasties were performed, of which 94,737 (56,9%) were primary THA. The total cost of the former was of BRL636,332,731.90 for SUS and there was an increase in the number of surgeries performed, especially from 2012. The annual average of primary THA was 11,842.1 surgeries/year (sd= 868.3 surgeries/year), at an average cost of BRL45,473,445.65/year (sd= BRL8,269,970.10/year).In 2012 the uncemented and hybrid arthroplasties became the most common. The distribution in the Brazilian states is heterogeneous and the factors positively associated were the % of citizens aging above 50 (p=0,000175) and the % of cities with high or very high HDI in each State (p=0,037). Conclusion: The incidence of primary THA in the SUS increased between 2008 and 2015. Its spatial distribution was greater on States with bigger proportions of people aging above 50 years and more cities with HDI rated as high or very high. The incidence of cemented primary THA was overcome by the uncemented and hybrid in 2012.

Analysis of the temporal performance of one versus on-line comprehensive two-dimensional liquid chromatography.

Our purpose is to generalize the chief conclusion of earlier studies based on complex maize seed extract samples that indicated that at very short times (less than 5 min) the peak capacity of 1D liquid chromatography was better than that of comprehensive, on-line 2D liquid chromatography (LC × LC), but that the LC × LC method begins to out-perform the 1D method at surprisingly short analysis times of only 5-10 min. We call the analysis time at which the peak capacities of 1D and LC × LC become equal the "crossover time." We quantify the importance of various system parameters such as the 1D peak capacity, the second dimension cycle time and second dimension peak capacity, and fractional coverage of the two-dimensional separation space on the crossover time of 1D versus LC × LC chromatography. For ranges of these parameters used in our earlier experimental studies, we believe that crossover times will generally be between 3 and 8 min under optimized on-line LC × LC conditions.

High performance liquid chromatographic method development for simultaneous analysis of doxofylline and montelukast sodium in a combined form.

AIM: Some literatures revealed that the high performance liquid chromatography (HPLC) method for single component or multicomponent analysis of montelukast sodium with other drugs. However, these methods deals with time consuming, so it is necessary to develop a cost-effective and less time consuming method for the estimation of doxofylline and montelukast sodium in combined pharmaceutical formulation. MATERIALS AND METHODS: The separation was performed on an inertsil C8 (5 µm, 4.6 × 250 mm) column in isocratic mode with the mobile phase consisting a mixture of methanol and sodium phosphate buffer (75:25 v/v, pH 6.5 adjusted with orthophosphoric acid). The mobile phase was pumped at a flow rate of 1 mL min(-1) and eluents were monitored at 230 nm. RESULTS: The selected chromatographic conditions were found to separate doxofylline (retention time = 3.4 min) and montelukast sodium (retention time = 5.5 min) with a resolution of 5.47. The proposed HPLC method was validated with respect to linearity, accuracy, repeatability, specificity, robustness, and ruggedness as per International Conference on Harmonisation guidelines Q2(R1), November 2005 (Validation of Analytical Procedures: Text and Methodology). The percentage recoveries for doxofylline and montelukast sodium ranged from 98.1% to 101.7% and 98.2 to 101.9%, respectively, which indicated that the above method was enough accurate and precise. CONCLUSIONS: Hence, it was concluded that the developed method is suitable for routine analysis of these combination due to its less analysis time.