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Open research questions in Analytical Chemistry and Chromatography

79 gap statements mined from Analytical Chemistry and Chromatography papers in our 4.5M-paper local library, which holds 588 papers on the topic — drawn mostly from each paper's own stated research gap, future-work, challenge and limitation notes, and its abstract. The ones listed below are a selection still marked open; each names the study that raised it, with a DOI link where the paper has one.

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What the literature leaves open

  • 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

  • The method needs to be efficient and environmentally friendly. The method needs to be validated as per FDA guidelines.

    A simultaneous LC–MS/MS assay for the quantification of xanomeline and trospium chloride in rat plasma: Method validation as per FDA guidelines and evaluation using green analytical chemistry principles and the blue tool · 2026 · DOI

  • 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 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

  • 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

  • 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.

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

  • 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 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

  • 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

  • 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

  • There is a need for environment-friendly and accurate analytical methods for pharmaceutical quality control. The existing methods may not demonstrate a favorable greenness profile.

    A Chromatographic Method Development and Validation for Tofacitinib Citrate and Baricitinib Using RGB And GREEN Pech · 2026 · DOI

  • Most published UPLC-MS/MS studies focus on final validation results without thoroughly explaining how the identified limitations were addressed during method development.

    A systematic stepwise optimization framework for rapid multi-analyte UPLC–MS/MS plasma analysis with integrated sustainability assessment · 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 pharmaceutical industry produces millions of liters of solvent waste every year, highlighting the need for more environmentally friendly methods. The review identifies the need for a more sustainable approach to chemical analysis.

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

  • First, derivatization addresses the fundamental limitation of electrospray ionization— namely, the inability to ionize neutral, non-basic, or non-acidic small molecules.

    From “Undetectable” to “Sensitive Detection”: Advances in Derivatization Techniques for LC-MS Analysis of Genotoxic Impurities · 2026 · DOI

  • Highly oxygenated organic molecules (HOMs) derived from monoterpenes are key precursors of secondary organic aerosols (SOA), yet their global-scale formation pathways and climate impacts remain poorly quantified due to uncertainties in autoxidation kinetics and branching ratios of peroxy radicals.

    A modeling study of global distribution and formation pathways of highly oxygenated organic molecules (HOMs) from monoterpenes · 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

  • 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

  • Looking ahead, pharmaceutical analysis is moving straight toward automation and miniaturization. Many laboratories are already upgrading from standard HPLC to Ultra-High-Performance Liquid Chromatography (UHPLC). By using columns packed with sub-2 µm particles, UHPLC can finish a run in under three minutes while cutting solvent consumption by up to 80%.

    GREEN ANALYTICAL CHEMISTRY AND QUALITY BY DESIGN APPROACHES IN RP-HPLC METHOD DEVELOPMENT AND VALIDATION: A COMPREHENSIVE REVIEW · 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 development of more sustainable and miniaturized enantioselective analytical platforms. The use of AI-assisted enantioselective analytical platforms.

    CHIRAL SEPARATION TECHNIQUES IN PHARMACEUTICAL ANALYSIS: CURRENT TRENDS AND FUTURE PERSPECTIVES · 2026 · DOI

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

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

  • Conventional pharmaceutical production has limitations in process behaviour monitoring, - There is a need for a preventive and knowledge-based quality…

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

  • Research on the NADES extraction mechanism. Optimization of the extraction process for other types of bioactive compounds. Investigation of the effects of different NADES on the extraction of phenolic compounds.

    Ultrasound-Assisted Extraction of Phenolic Compounds from Celtuce (Lactuca sativa var. augustana) Leaves Using Natural Deep Eutectic Solvents (NADES): Process Optimization and Extraction Mechanism Research · 2024 · DOI

Most-cited papers in Analytical Chemistry and Chromatography

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Open questions raised by papers listed on this page include: (1) 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…”, 2026); (2) The lack of integration of GAC, BAC, and WAC principles in HPTLC (“Sustainable advancement of high-performance thin-layer chromatography:…”, 2026); (3) Future research should focus on developing more sensitive and specific analytical methods for impurity profiling (“A COMPREHENSIVE REVIEW OF RP-HPLC TECHNIQUES FOR IMPURITY PROFILING IN…”, 2026); (4) There is a need for a sensitive and efficient method for detecting the S-enantiomer of linagliptin (“Determination of S‐enantiomer in linagliptin by supercritical fluid…”, 2026); (5) There is a need for a simple and reliable method for paracetamol quantification (“THREE-WAY DATA ANALYSIS OF COPPER-PARACETAMOL COMPLEX FORMATION FOR THE…”, 2026). 79 gap statements have been mined from Analytical Chemistry and Chromatography papers in our 4.5M-paper local library, which holds 588 papers on the topic; the gaps come from whichever of those papers state one. They are mostly the research gaps the authors state and the papers' abstracts, plus future-work, limitations and challenges passages. The ones listed below are a selection still marked open; each names the study that raised it, with a DOI link where the paper has one, so you can read the original claim in context.

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