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Open research questions in Analytical Chemistry and Chromatography

57 unresolved questions extracted from the limitations and future-work sections of 299 Analytical Chemistry and Chromatography papers in our library. Each links back to the study that raised it.

What the literature leaves open

  • One of the challenges is the presence of impurities in active pharmaceutical ingredients (APIs) and finished dosage forms. Another challenge is the need for accurate impurity analysis to minimize potential health risks and to maintain the safety profile of pharmaceutical products. The complexity of pharmaceutical formulations and the variety of potential impurities also pose a challenge.

    A COMPREHENSIVE REVIEW OF RP-HPLC TECHNIQUES FOR IMPURITY PROFILING IN PHARMACEUTICAL DRUG ANALYSIS · 2026 · DOI

  • Future research should focus on developing more sensitive and specific analytical methods for impurity profiling. Future research should also investigate the use of other techniques, such as mass spectrometry, for impurity profiling.

    A COMPREHENSIVE REVIEW OF RP-HPLC TECHNIQUES FOR IMPURITY PROFILING IN PHARMACEUTICAL DRUG ANALYSIS · 2026 · DOI

  • There is a need for a precise, reliable, and practical analytical approach for teicoplanin quantification. Current methods have limitations and challenges.

    ADVANCES IN ANALYTICAL METHODS FOR TEICOPLANIN QUANTIFICATION: FOCUS ON HLPC-UV, LC-MS/MS, AND INNOVATIVE SAMPLE PREPARATION STRATEGIES: A COMPREHENSIVE REVIEW · 2026 · DOI

  • The use of harmful chemicals in chemical analysis is a significant challenge. The production of millions of liters of solvent waste every year is a major environmental concern. The need for more sustainable approaches to chemical analysis is a key challenge.

    GREEN ANALYTICAL CHEMISTRY: AN ECO-FRIENDLY APPROACH TO PHARMACEUTICAL · 2026 · DOI

  • Limited information about process behaviour, - Difficulty in identifying and prioritizing risks, - Need for a preventive and knowledge-based quality system

    A REVIEW ON PROCESS ANALYTICAL TECHNOLOGY (PAT): APPLICATIONS IN QUALITY ASSURANCE OF PHARMACEUTICAL MANUFACTURING · 2026 · DOI

  • Development • AI models depend on the quality and availability of historical chromatographic data, which may limit prediction accuracy. • Performance may be reduced for novel or structurally unique compounds not included in training datasets. • Implementation requires technical expertise in both chromatography and data science. • Some AI models prediction rationale difficult to explain. • Experimental validation is still necessary to confirm AI-predicted conditions. • Regulatory development is still evolving.

    AI-ASSISTED VERSUS CONVENTIONAL HPLC METHOD DEVELOPMENT FOR PHARMACEUTICAL PREPARATIONS: A COMPARATIVE STUDY · 2026 · DOI

  • Future research should focus on developing more efficient and cost-effective RP-HPLC methods for pharmaceutical dosage forms. There is a need for further studies on the application of Ultra-Performance Liquid Chromatography (UPLC) in the pharmaceutical sector. The development of new column technologies and solvent systems could improve the efficiency and robustness of RP-HPLC methods.

    REVERSED-PHASE HIGH-PERFORMANCE LIQUID CHROMATOGRAPHY (RP- HPLC) BASED ANALYTICAL METHOD DEVELOPMENT AND VALIDATION FOR PHARMACEUTICAL DOSAGE FORMS: A COMPREHENSIVE REVIEW · 2026 · DOI

  • The pharmaceutical industry requires highly reliable analytical techniques to ensure product safety and clinical efficacy. There is a need for a comprehensive review of RP-HPLC method development and validation for pharmaceutical dosage forms. The industry is shifting away from traditional trial-and-error testing toward Analytical Quality by Design (AQbD).

    REVERSED-PHASE HIGH-PERFORMANCE LIQUID CHROMATOGRAPHY (RP- HPLC) BASED ANALYTICAL METHOD DEVELOPMENT AND VALIDATION FOR PHARMACEUTICAL DOSAGE FORMS: A COMPREHENSIVE REVIEW · 2026 · DOI

  • Scalability limitations and instrument compatibility issues hinder widespread implementation of green HPTLC and HPLC methods. Variations in solvent properties and increased system backpressure can limit flow rate flexibility and reduce column lifespan. The lack of standardized evaluation frameworks and regulatory guidelines restricts the acceptance and transferability of green analytical methods.

    GREEN HPTLC AND HPLC: CHALLENGES IN STANDARDIZATION AND PRACTICAL IMPLEMENTATION IN PHARMACEUTICAL ANALYSIS · 2026 · DOI

  • The development of standardized evaluation frameworks for green analytical methods. The application of Life Cycle Assessment (LCA) for evaluating the environmental impact of chromatographic methods. The exploration of new eco-friendly solvents and optimized chromatographic conditions for green HPTLC and HPLC methods.

    GREEN HPTLC AND HPLC: CHALLENGES IN STANDARDIZATION AND PRACTICAL IMPLEMENTATION IN PHARMACEUTICAL ANALYSIS · 2026 · DOI

  • The need for more sensitive and selective analytical techniques. The challenge of detecting and identifying unknown impurities. The importance of regulatory expectations from ICH guidelines.

    ADVANCED CHROMATOGRAPHIC STRATEGIES FOR ASSAY, PURITY, AND IMPURITY CONTROL IN PHARMACEUTICAL DRUG SUBSTANCES AND PRODUCTS · 2026 · DOI

  • Limited life-cycle assessments (LCA). Trace sensitivity. Digital standardization.

    Sustainable advancement of high-performance thin-layer chromatography: integrating green, blue and white analytical chemistry with smart software solutions · 2026 · DOI

  • The need for sustainable and environmentally responsible analytical practices in HPTLC. The lack of integration of GAC, BAC, and WAC principles in HPTLC. The limited application of greenness and whiteness assessment tools to HPTLC methods.

    Sustainable advancement of high-performance thin-layer chromatography: integrating green, blue and white analytical chemistry with smart software solutions · 2026 · DOI

  • A lack of commercially available or suitable racks for gravity-driven column chromatography. Many laboratories rely on improvised or custom-built solutions that are inefficient in their use of fume-hood space.

    Laser-cut and 3D Printed Gravity-Driven Chromatography Column Rack and Vial Holders · 2026 · DOI

  • Future developments may include scaling the rack for different numbers of columns, adapting aperture sizes for alternative column geometries, and substituting construction materials to improve solvent resistance. Community-driven iteration and adaptation are encouraged. Paper Author Contributions (CRediT) Conceptualisation: C.A.W-T Design and fabrication: E.V. Testing and validation: C.A.W-T Manuscript writing: C.A.W-T and E.V.

    Laser-cut and 3D Printed Gravity-Driven Chromatography Column Rack and Vial Holders · 2026 · DOI

  • Practical limitations of AI-assisted impurity analysis include the need for large datasets and the potential for human error in data interpretation. Green Chemistry Optimization and Federated Learning are potential limitations and areas for future research.

    AI-Assisted Identification and Quantification of Pharmaceutical Impurities using HPLC Chromatographic Data · 2026 · DOI

  • The application of Green Chemistry Optimization and Federated Learning to AI-assisted impurity analysis. The development of more advanced machine learning models for automated quantification and peak recognition.

    AI-Assisted Identification and Quantification of Pharmaceutical Impurities using HPLC Chromatographic Data · 2026 · DOI

  • To investigate the effect of the S-enantiomer on the efficacy and safety of linagliptin. To apply the method to other chiral drugs. To further optimize the method for improved sensitivity and efficiency.

    Determination of S‐enantiomer in linagliptin by supercritical fluid chromatography-ultraviolet detection · 2026 · DOI

  • There is a need for a sensitive and efficient method for detecting the S-enantiomer of linagliptin. Prior methods have limitations in terms of sensitivity and efficiency.

    Determination of S‐enantiomer in linagliptin by supercritical fluid chromatography-ultraviolet detection · 2026 · DOI

  • There is a lack of understanding of the composition of acidic oxygenated compounds in Bulla-deniz condensate. Prior studies have not examined the structure-group composition of acidic oxygenated compounds in Bulla-deniz condensate.

    STUDY OF ACIDIC OXYGEN-CONTAINING COMPOUNDS OF BULLA-DENIZ CONDENSATE · 2026 · DOI

  • Existing methods for paracetamol quantification may have limitations in terms of complexity and cost. There is a need for a simple and reliable method for paracetamol quantification.

    THREE-WAY DATA ANALYSIS OF COPPER-PARACETAMOL COMPLEX FORMATION FOR THE QUANTIFICATION OF PARACETAMOL IN PHARMACEUTICAL MATRICES · 2026 · DOI

  • The related substances and polymers of biapenem must be strictly controlled. There is a need for a reliable tool for structural analysis of the impurities of biapenem.

    Fragmentation pathways of biapenem and its impurities using high performance liquid chromatography quadrupole time of flight tandem mass spectrometry · 2026 · DOI

  • However, the structures of some of the impurities, such as Impurity IX, could not be determined by MS, and MS lacks of the ability of confirming the configuration of the impurities, so NMR is required in order to confirm the impurity structure and its configuration after purification.

    Fragmentation pathways of biapenem and its impurities using high performance liquid chromatography quadrupole time of flight tandem mass spectrometry · 2026 · DOI

  • The existing systems for registering signals from liquid crystal sensors have limited accuracy due to illumination source instability and external factors. There is a need for a system that can improve measurement reliability and stability.

    Dual-channel optical signal registration system for a liquid crystal gas sensor · 2026 · DOI

  • The paper identifies the need for a comprehensive review of RP-HPLC method development and validation. The authors highlight the growing use of Analytical Quality by Design (AQbD) to create reliable Method Operable Design Regions (MODR).

    GREEN ANALYTICAL CHEMISTRY AND QUALITY BY DESIGN APPROACHES IN RP-HPLC METHOD DEVELOPMENT AND VALIDATION: A COMPREHENSIVE REVIEW · 2026 · DOI

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57 open questions have been extracted from the limitations and future-work passages of 299 Analytical Chemistry and Chromatography papers in our library. Each one below links back to the study that raised it, so you can read the original claim in context.

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