Cost Control Research Articles

Enabling Multi-Step Forecasting with Structured State Space Learning Module

Data-driven soft sensor incorporated with the model predictive control (MPC) algorithms facilitating product quality and cost control are of imperative importance in industrial processes. However, the widely used one-step forecasting method can not incorporate with MPC and therefore restricts the practical usage of soft sensor. Multi-step forecasting introduces long-term dependencies problems yet has not been effectively resolved within traditional model structure. To address this problem, this paper proposes the deep learning network architecture named Extended State Space Learning Module (ESSLM). ESSLM extends the nonlinear mapping architecture of deep learning based on state space and retains state transfer matrices to characterize the dynamics of the system. ESSLM distinguishes itself from explicit network architectures such as gated RNNs by addressing the long-term dependencies problems through an implicit initialization method, and the MLP and RNN algorithms can be regarded as the manifestation of ESSLM in special cases. ESSLM characterizes the latent space as the coefficients of the orthogonal basis functions so that the input data can be encoded into a high-dimensional feature space with minimal information loss which efficiently achieves multi-step forecasting and give greater utility and practical significance.

The influence of imidacloprid seed treatment on non-ThryvOn and ThryvOn cotton.

In the southern United States, thrips are a significant early season pest of cotton. In the United States, in 2022, 98% of cotton acres were infested with thrips, and, of those acres, 45% were treated for thrips. Thrips injury resulted in over $113 million dollars in losses plus control costs to the cotton industry in the United States that year. A new Bacillus thuringiensis trait known as ThryvOn has been commercialized to provide control against thrips. There is ongoing debate about the need for an insecticidal seed treatment to improve thrips control on ThryvOn varieties. Field studies were conducted to determine if the addition of an imidacloprid seed treatment improved efficacy against tobacco thrips and to determine if reduced rates of seed treatments (0, 25, 50, 75, and 100% of the labeled rate) provided benefits for thrips control in ThryvOn cotton. To control for infestation pressure, a complementary greenhouse study was conducted using the same treatments under controlled conditions. Imidacloprid provided only a limited benefit for improved management on ThryvOn cotton in the greenhouse study, but no benefit in the field study. Efforts in pest surveillance should be continued in ThryvOn cotton to allow for foliar applications when warranted based on established thresholds. No conclusions can be drawn about the benefits of an imidacloprid seed treatment for resistance management in ThryvOn cotton from this study, but these data suggest that any benefit would be minimal.

On Uniform Null Controllability of Transport–Diffusion Equations With Vanishing Viscosity Limit

ABSTRACTThis paper aims to address an interesting open problem, posed in the paper “Singular Optimal Control for a Transport‐Diffusion Equation” of Sergio Guerrero and Gilles Lebeau in 2007. The problem involves studying the null controllability cost of a transport–diffusion equation with Neumann conditions, where the diffusivity coefficient is denoted by and the velocity by . Our objective is twofold. First, we investigate the scenario where each velocity trajectory originating from enters the control region in a shorter time at a fixed entry time. By employing Agmon and dissipation inequalities, and Carleman estimate in the case is the gradient of a time‐dependent scalar field, we establish that the control cost remains bounded for sufficiently small and large control time. Secondly, we explore the case where at least one trajectory fails to enter the control region and remains in . In this scenario, we prove that the control cost explodes exponentially when the diffusivity approaches zero and the control time is sufficiently small for general velocity.

Strategic procurement practices in healthcare organizations and their impact on Medicaid and Medicare cost containment

Strategic procurement in healthcare organizations has emerged as a critical factor in addressing the escalating costs within Medicaid and Medicare programs. This comprehensive review synthesizes current literature and empirical evidence on innovative procurement practices and their impact on healthcare cost containment. Through extensive analysis of procurement transformation across healthcare organizations, this review identifies key trends in value-based purchasing, digital integration, and supply chain optimization. Findings indicate that healthcare organizations implementing strategic procurement practices achieve substantial cost reductions in medical supplies and equipment while maintaining or improving quality standards. The integration of artificial intelligence and blockchain technologies in procurement processes has demonstrated particular promise, with early adopters reporting enhanced transparency and reduced administrative burden. This review also reveals significant barriers to implementation, including organizational resistance, regulatory constraints, and technical infrastructure limitations. The findings suggest that successful procurement transformation requires a systematic approach combining technological innovation, organizational change management, and policy adaptation. These insights provide valuable guidance for healthcare administrators, policymakers, and researchers working to optimize healthcare resource allocation and control costs in public health insurance programs.

P-1293. Healthcare Costs Associated with Lyme Disease in a US Insured Population

Abstract Background An estimated 476,000 people are diagnosed and treated for Lyme disease (LD) each year in the United States (US). LD manifests as localized (e.g., single erythema migrans (EM)) or disseminated disease (e.g., multiple EM, arthritis, cardiac, and neurologic conditions). Healthcare costs for LD patients by clinical manifestation are understudied. This work aimed to assess costs of LD by manifestation in an insured US population. Methods This retrospective study identified LD patients in the Optum Market Clarity Integrated Claims and Clinical dataset from January 2016 through December 2022 based on LD diagnosis codes (A69.xx). Outpatient LD patients had claims for relevant antibiotics within 30 days of diagnosis. Inpatient LD patients had LD as a primary or secondary diagnosis with a LD-associated condition as primary. Cases were classified as disseminated, localized, or undetermined based on diagnosis codes for LD and LD-associated conditions, inpatient vs. outpatient services, and antibiotic treatment. Healthcare costs were assessed for 1) LD-specific costs during individual LD episodes, 2) all-cause 6-month follow-up costs vs. baseline costs for LD patients, 3) all-cause 6-month follow-up costs for LD vs. controls (matched 3:1 to cases by hard matching and propensity score matching on demographic and clinical characteristics). Costs were standardized across payer types and CPI-adjusted to 2022. Results During 2016-2022, 70,531 LD cases (mean age 45 years, 51% female) were identified. Mean (standard deviation) LD-specific total medical costs were $2,227 ($15,790) per episode, with $695 ($7,348) and $6,833 ($27,983) for localized and disseminated cases, respectively (Figure 1). Compared with a 6-month baseline, mean all-cause total costs during 6-month follow-up were $3,304 greater for LD diagnosed patients overall, $1,381 greater for localized, and $10,130 greater for disseminated (Figure 2). Compared to controls, mean total all-cause 6-month follow-up costs were greater by $4,098 for LD overall, $819 for localized, and $12,978 for disseminated (Figure 3). Conclusion Patients diagnosed with LD incurred substantial costs, driven by disseminated disease. This poses a large economic burden to the healthcare system. Effective preventive measures are needed. Disclosures Rebecca M. Fee, MPH, Optum: Employee Holly Yu, MSPH, Pfizer: Employee|Pfizer: Stocks/Bonds (Public Company) L. Hannah Gould, PhD, MS, MBA, Pfizer: Employee|Pfizer: Stocks/Bonds (Public Company) Amanda R. Mercadante, PharmD, Pfizer, Inc.: Stocks/Bonds (Public Company) Brian T. Campfield, MD, Pfizer: Advisor/Consultant John Halperin, MD, Abbott: Stocks/Bonds (Public Company)|Abbvie: Stocks/Bonds (Public Company)|Johnson & Johnson: Stocks/Bonds (Public Company)|Merck: Stocks/Bonds (Public Company)|Pfizer: Advisor/Consultant Mary G. Johnson, PharmD, MSPH, UHG/Optum: Employee|UHG/Optum: Stocks/Bonds (Public Company) Benjamin Chastek, MS, Optum: Employee|Optum: Stocks/Bonds (Public Company)

Total Cost of Ownership and Evaluation of Google Cloud Resources for the ATLAS Experiment at the LHC

The ATLAS Google Project was established as part of an ongoing evaluation of the use of commercial clouds by the ATLAS Collaboration, in anticipation of the potential future adoption of such resources by WLCG grid sites to fulfil or complement their computing pledges. Seamless integration of Google cloud resources into the worldwide ATLAS distributed computing infrastructure was achieved at large scale and for an extended period of time, and hence cloud resources are shown to be an effective mechanism to provide additional, flexible computing capacity to ATLAS. For the first time a total cost of ownership analysis has been performed, to identify the dominant cost drivers and explore effective mechanisms for cost control. Network usage significantly impacts the costs of certain ATLAS workflows, underscoring the importance of implementing such mechanisms. Resource bursting has been successfully demonstrated, whilst exposing the true cost of this type of activity. A follow-up to the project is underway to investigate methods for improving the integration of cloud resources in data-intensive distributed computing environments and reducing costs related to network connectivity, which represents the primary expense when extensively utilising cloud resources.

Application of Cost Control Techniques in Construction Projects Delivery

Purpose: This research work deals on the application of cost control techniques in Construction project delivery. The need for the work arose as projects suffer from cost and time overruns due to factors stemming from poor cost control during at the design and execution stages of Construction projects. Material and Methods: This study adopted an exploratory research design using a structured questionnaire as the primary instrument for data collection. The research was conducted in Rivers State, Nigeria, known for its robust infrastructure development and relevance to the construction sector. The study population comprised public and private contractors, including civil engineers and quantity surveyors. A random sampling technique was employed to select 50 contractors, considering time and financial constraints. Findings: The analysis of the data obtained from the respondents identified cost control techniques that include schedules, budgeting, inspection, meetings, reports, records, monitoring & evaluations, as the commonly used techniques for cost control. The study also revealed that most project managers and contractors in Port Harcourt find it difficult in controlling project costs due to problems which include delays by clients to release fund as at when due, indecision, lack of materials and equipment, bad weather, overlapping of activities, unclear and incomplete drawings, making good defective works, and generally failure to control the productivity of resources. Others of paucity were due to theft and vandalism, interference by clients, high labor turnover, and insufficient knowledge on cost control techniques. Implications to Theory, Practice and Policy : The study therefore recommends proper knowledge and application of cost control techniques, adequate management of the cost control techniques, good site organization and reporting and adequate supervision of Construction projects should be adopted and implemented.

Mid- to long-term clinical outcomes of modified technique skip-level titanium plate fixation in cervical laminoplasty compared to continuous fixation

PurposeTo compare the efficacy and safety of skip titanium plates combined with adjacent spinous process suture suspension versus continuous titanium plate fixation in cervical laminoplasty.MethodsA retrospective analysis of 125 patients (62 men, 63 women, average age 60.9 ± 10.4 years) with multilevel cervical spondylotic myelopathy who had cervical laminoplasty with Arch titanium plate fixation from January 2012 to March 2024 in our hospital was done. Patients were stratified into two cohorts based on the fixation technique: Group A (n = 64): Modified technique of skip-level titanium plate fixation (Arch titanium plates at C4 and C6 levels combined with adjacent spinous process suture suspension)Group B (n = 61): Continuous plating (Arch titanium plates applied sequentially from C3 to C7).The comparative analysis focused on perioperative parameters (operative duration, intraoperative blood loss, length of hospital stay), economic factors (hospital costs), and various clinical indicators.ResultsThe average follow up period was (73.0 ± 38.4) months. Both groups showed no significant differences in gender, age, and disease duration (P > 0.05). Group A had lower hospitalization costs, intraoperative blood loss, operation time, and postoperative hospital stay compared to Group B (P < 0.05). Postoperatively, both groups had significant improvements in JOA scores and NDI (P < 0.005), but there were no significant differences in postoperative scores and improvement rates between the two groups (P > 0.05). At 3 months postoperatively and at the last follow-up, the C2-7 Cobb angle and cervical curvature index decreased compared to preoperative values (P < 0.05), with a significant difference in the C2-7 Cobb angle at the last follow-up (P < 0.05). The sagittal diameter of the spinal canal from C3 to C7 significantly increased (P < 0.05), but there were no significant differences in the improvement of C3, C5, and C7 between the two groups (P > 0.05). At 3 months postoperatively, the opening angles of the C4 and C6 laminae in Group A were smaller than those in Group B (P < 0.05), but there were no significant differences at the last follow-up (P > 0.05). The healing of the C4 and C6 laminae in Group B was superior to that in Group A (P < 0.05), but there were no differences in healing at the last follow-up (P > 0.05). The incidence of axial symptoms was similar (10.9% in Group A and 14.8% in Group B, P = 0.523).ConclusionsDuring C3-7 laminoplasty, the clinical efficacy of the method combining mini titanium plate fixation (at C4 and C6) with suture fixation is comparable to that of continuous fixation. Moreover, it has an advantage in cost control.

Pengendalian Biaya Produksi dalam Manufaktur: Teknik dan Tantangan

Controlling production costs in manufacturing is a crucial aspect that influences a company's efficiency and profitability. This research discusses various strategies and best practices in cost control, including analysis of raw material, labor and overhead costs. By implementing lean manufacturing principles, companies can identify and reduce waste, and increase productivity. Additionally, the use of technology and automation can contribute to long-term cost reduction. Implementation of a quality control system that has also been proven to reduce defect costs and increase customer satisfaction. Through regular performance evaluations and continuous innovation, companies can optimize production processes and achieve competitive advantage. This research is expected to provide insight for practitioners and academics in understanding the importance of controlling production costs in manufacturing.

MENINGKATKAN EFISIENSI ORGANISASI: PERAN KLASIFIKASI BIAYA DALAM PENGAMBILAN KEPUTUSAN

This study explores the role of cost classification in improving organizational efficiency and its impact on decision-making processes. The primary objective is to analyze how accurate cost classification aids managers in understanding fixed, variable, direct, and indirect costs to make more informed financial decisions. By employing effective cost control and budget planning strategies, organizations can better manage their resources, reduce unnecessary expenditures, and improve overall performance. This research utilizes a case study approach to highlight practical examples of how cost classification directly contributes to operational efficiency. The findings indicate that proper cost classification not only facilitates decision-making but also enhances competitiveness in a highly dynamic market. Recommendations are provided to help organizations integrate cost classification into their financial management systems for sustainable growth.

Static output feedback strategy for mean-field social control with nonlinear stochastic dynamics

A mean-field social control problem for uncertain nonlinear stochastic systems is investigated by using a robust static output feedback (SOF) strategy. First, the problem in the single decision maker case is investigated in terms of guaranteed cost control approaches to derive suboptimal conditions at the supremum of the cost function. The Karush-Kuhn-Tucker (KKT) condition is used to derive the necessary conditions which are expressed as a large stochastic combined matrix equation (SCME). Second, the preliminary results in the single decision maker case are used to study the Pareto optimal strategy in a cooperative game. As our main contribution, we derive the high-order centralised strategies and the low-order decentralised strategies, respectively, for the cooperative game. In order to avoid the difficulty of higher-order dimensional problem related to SCMEs, a new reduced-order decomposition numerical scheme by means of Newton's method is developed. The computation for designing the proposed strategy set can be performed in low dimension, even when the number of decision makers approachs to infinity. Moreover, the degradation of the cost function is rigorously evaluated by comparing the centralised strategy set with the proposed strategy set. Finally, several numerical experiments are conducted to demonstrate the usefulness and effectiveness of the proposed strategy set.

Digital transformation and pathways for promoting global value position: an empirical study in Chinese manufacturing industries

Abstract Digital transformation offers new avenues for the photovoltaic manufacturing industry and his paper, grounded in value chain theory, collaborative management theory, and value chain cost control theory, examines digital transformation through three key dimensions: process optimization, platform ecosystem development, and data-driven strategies. The results show that digital transformation has effectively streamlined R&amp;D, procurement, production, and sales costs. Notably, the R&amp;D expenditure as a percentage of operating income decreased from around 4.2% to 3.1%. Furthermore, after digital transformation, significant improvements were seen in supplier delivery qualification rates, market share, and customer satisfaction.

Semaglutide 2.4 mg versus Liraglutide 3 mg for the Treatment of Obesity in Greece: A Short-Term Cost-Effectiveness Analysis.

Obesity is a global health issue with significant economic implications for health systems. Pharmacotherapy, including semaglutide 2.4 mg and liraglutide 3 mg, offers a treatment option for weight management; however, its cost-effectiveness requires evaluation. This study assesses the short-term cost-effectiveness of semaglutide 2.4 mg versus liraglutide 3 mg in achieving clinically relevant weight loss targets at 68 weeks in Greece. A short-term cost-effectiveness analysis was conducted from the perspective of the Greek third-party payer [National Organization for the Provision of Health Services (EOPYY)], comparing costs and outcomes for semaglutide 2.4 mg and liraglutide 3 mg over a 68-week horizon. Effectiveness was measured by the proportion of patients achieving weight loss targets of ≥ 5%, ≥ 10%, ≥ 15%, and ≥ 20%, using efficacy data from the STEP-8 head-to-head trial, a 68-week, randomized, double-blind study conducted in the USA, comparing semaglutide 2.4 mg versus liraglutide 3 mg in adults who were overweight or had obesity without diabetes. Only direct medical costs were included, reflecting the payer perspective, and no discounting was applied owing to the short time horizon. Deterministic and probabilistic sensitivity analyses assessed the results' robustness. Semaglutide 2.4 mg had higher treatment costs (€3285.55) compared with liraglutide 3 mg (€2742.47) but demonstrated greater efficacy and a lower cost of control across all weight loss targets. The cost per patient achieving ≥ 5% weight loss was €3768.72 for semaglutide and €4718.66 for liraglutide, corresponding to a difference of €949.95 per patient. The cost difference widened at higher weight loss targets, with semaglutide showing differences of €6064.20 for ≥ 10% weight loss, €17,005.23 for ≥ 15%, and €37,296.00 for ≥ 20%. These findings were consistent across sensitivity analyses. Semaglutide 2.4 mg is likely to be a short-term, cost-effective treatment option for adults who are overweight or have obesity without diabetes in Greece.

Pricing for Multi-Indication Drugs in the Italian Regulatory Context.

The authorization of new therapeutic indications for drugs already reimbursed by the Italian National Health Service (NHS) represents a matter of importance. This study aims to estimate the additional discount attributed to the extension of indications (EoIs) to explore the potential correlation between spending and negotiated discounts and to find specific factors (determinants) that impact on discount. The study focused on drugs approved in Italy between 2003 and 2017 with at least four therapeutic indications, including the first approved and EoIs, with follow-up extended until 2021 to acquire all the information on the negotiation process that has been completed. Data were obtained from reimbursement and pricing dossiers, and negotiation assessments. Trends in the number of EoIs submitted and the additional discounts negotiated were analyzed, along with the relationship between the negotiated discount and subsequent drug expenditure. Determinants influencing the extent of the negotiated discount were assessed, including drug type, orphan drug designation, innovativeness status, number of EoIs, disease incidence and prevalence, estimated number of patients, revenue projections, availability of therapeutic alternatives, and efficacy outcomes. A Wilcoxon nonparametric test was used to evaluate the associations between determinants and the negotiated additional discount, with a significance level of 0.05. The study identified nine medicines: five of these were used in onco-hematologic therapeutic areas, while the remaining four were immunosuppressants for dermatologic and/or rheumatologic conditions. These nine active substances accounted for 65 approved therapeutic indications, of which 50 were reimbursed by the Italian NHS, including the first indication; the analysis focused only on 40 reimbursed EoIs. The additional discount obtained for EoIs averages approximately 12.5% (95% CI 9.4-16.6%), with a median value of approximately 11%. This latter value was used as the threshold in the analysis of the determinants potentially impacting the negotiated discount amount. Discounts greater than 11% were significantly associated with EoI beyond the fifth and oncology drugs. The additional discount seemed small when compared with the increased spending. AML seems to incur substantial direct economic expenses. Reducing the days of hospitalization can significantly decrease the economic burden of AML in the European Union. Moreover, there is a necessity for studies that comprehensively evaluate the economic implications, particularly concerning total and indirect costs. The study provides valuable insights into the negotiation outcomes for medicines with multiple therapeutic indications, particularly in onco-hematologic and immunosuppressive areas. The analysis revealed that additional discounts for EoIs averaged 12.5%, with a median of 11%, a value used to assess the impact of specific determinants. A discount higher than 11% was statistically correlated with drugs having more than five indications and oncology treatments, showing their influence in negotiations. However, the savings from discounts were modest relative to the increased drug spending as more indications were approved. This suggests an imbalance between the cost control achieved through discounts and the rising expenditure due to expanded drug use.

Performance Evaluation of Time and Cost In The Bungur-Kedoyo Tulungagung Road Construction Project Using The Earned Value Method

Road infrastructure is essential for supporting transportation, fostering economic growth, and enhancing community mobility. However, the Bungur-Kedoyo road construction project in Tulungagung has faced challenges in time and cost management, impacting overall project performance. This study aims to evaluate the project's time and cost performance using the Earned Value Method (EVM), a robust tool that compares planned work, completed work, and actual costs to provide a comprehensive performance analysis. Data from the 25th-week project report revealed delays, with a Schedule Variance (SV) of -Rp. 315,481,514.90 and a Schedule Performance Index (SPI) of 0.970, indicating slower progress than initially planned (SPI &lt; 1). These results highlight the need for improved project scheduling and enhanced control mechanisms to mitigate delays and manage costs effectively. By identifying inefficiencies and areas requiring intervention, the study provides actionable recommendations for improving project management practices. It concludes that integrating EVM into time and cost control processes can significantly enhance project efficiency and reliability. This research contributes to advancing infrastructure development by offering insights that can be applied to similar projects, ensuring timely and cost-effective delivery while promoting sustainable growth in the road construction sector.

Cost Control System Analysis of Hero and Bajaj Two-Wheeler Automobile Companies in India: A Comparative Study

Cost Control System Analysis of Hero and Bajaj Two-Wheeler Automobile Companies in India: A Comparative Study

Research on the Green Path of Building Electrical Engineering in the Context of Digitalization

In today's digital era, the greening of building electrical systems has become a crucial path for the sustainable development of the construction industry. Judging from the current research status at home and abroad, although certain achievements have been made, there are still many areas that need further exploration. Digital technologies have brought transformative opportunities to building electrical systems. In the field of intelligent lighting, they can achieve precise dimming and scene adaptive control; in the application of high-efficiency and energy-saving equipment, their performance can be optimized with the help of digital monitoring and regulation; after the digital upgrade of energy management systems, refined energy consumption analysis and intelligent dispatching can be accomplished; in the process of integrating renewable energy with building electrical systems, digital technologies can help solve the problems of intermittency and stability. However, this process is faced with challenges such as technology integration, cost control, standards and regulations, and user awareness. Looking ahead, with technological innovation and policy promotion, the greening of building electrical systems will thrive in the directions of intelligence, high efficiency, and synergy, laying a solid theoretical and practical foundation for the sustainable development in the construction field.

Analysis and Optimization of the Value Chain of H Logistics Company

This paper studies the current situation, problems, and optimization strategies of the value chain of H Logistics Company. With the gradual development of the logistics industry, its status has been continuously improved, and value chain optimization has become an important means to enhance the competitiveness of logistics enterprises. Based on the value chain theory proposed by Michael Porter, this paper comprehensively analyzes the core links of H Logistics Company such as procurement, warehousing, transportation, and distribution, finds out its problems in supplier management, warehousing resource allocation, transportation cost control, and service quality improvement, and proposes targeted optimization measures. In the procurement link, H Logistics Company has problems with a supplier evaluation system, poor cost control, and lagging in information construction. It is recommended that a supplier rating mechanism be introduced, refined expense management be strengthened, and information on the procurement process be promoted. In the warehousing link, low resource utilization, poor classification management efficiency, and insufficient technical investment are the main problems. Countermeasures such as optimizing warehouse layout, adopting intelligent sorting equipment, and strengthening employee training are proposed. In the transportation and distribution link, the company has shortcomings in logistics network planning, vehicle scheduling, and service quality. It is recommended to improve it through intelligent path optimization, dynamic allocation of transportation capacity, and promotion of green logistics. This study not only provides a specific path for H Logistics Company to improve operational efficiency but also provides a direction for value chain management in the logistics industry. Optimizing the value chain can not only improve the internal operational efficiency of the enterprise but also achieve cost savings, improved customer satisfaction, and enhanced competitiveness in the market environment, laying the foundation for the sustainable development of the logistics industry.

Optimal Risk Control of Complex Supply Chain Networks under Public Emergencies

Public emergency is an event that occurs suddenly, has a wide range of influence, and brings great impact to the society. It has the characteristics of suddenness, publicity, urgency and uncertainty. Frequent public emergencies pose a great threat to supply chain security, causing serious economic losses and social impacts. In order to improve the ability of supply chain network to cope with public emergencies, it is of great significance to study the law of supply chain risk transmission and risk control measures. Through the review of the relevant theories of supply chain sudden risk and infectious disease model, the existing problems and research prospects are pointed out. Then, based on the SEIR model, a complex supply chain network risk control model under government intervention is constructed to explore the transmission mechanism of supply chain risk and the optimal control rate of the government. Finally, the simulation verifies that by controlling the basic reproduction number, the government can effectively curb the further spread and diffusion of risks, and achieve the goal of controlling risks and balancing cost control.

Automatic monitoring and on-line chiral separation of chiral drug synthesis.

Chiral synthesis of single chiral drugs offers high efficiency, controllable costs, and excellent enantioselectivity, making it crucial in the pharmaceutical industry. A significant number of studies on chiral drug synthesis primarily focuses on the design and synthesis of innovative chiral catalysts and ligands with extremely high selectivity, as well as the development of new methods and strategies. Nonetheless, the on-line monitoring of chiral drug synthesis and its underlying mechanisms remain obscure. The principal challenge lies in the diverse synthesis pathways and intricate mechanisms of chiral drugs, with numerous intermediates and by-products. To tackle this issue, employing the chiral drug omeprazole as a breakthrough, we design and establish a reliable and stable analytical method to monitor the synthesis process. By integrating electrokinetic chromatography technology with automatic sequence injection, the chiral synthesis of omeprazole can be comprehensively tracked and monitored throughout its entire process. During the chiral drug synthesis process, all compounds, containing all reagents and products (omeprazole sulfide, R-omeprazole, S-omeprazole, iodobenzene and iodobenzene diacetate) are efficiently separated and simultaneously detected through a single run. The method shows a high resolution greater than 1.2, a wide linear range with a detection limit as low as 0.008 μM, as well as exceptional repeatability in sequence analysis. Therefore, the proposed method has demonstrated significant value in the analysis of chiral drug synthesis and holds potential for extensive application in the industrial production of chiral compound synthesis.