Miniaturized sample preparation and analytical strategies for cannabis and cannabinoid analysis

Abstract

Background: Global expansion of medicinal and recreational cannabis markets has created an increasingly diverse range of products, intensifying demand for analytical methodologies that are accurate, high-throughput, environmentally sustainable, and adaptable to complex matrices. Cannabis poses unique analytical challenges owing to its chemically diverse phytochemical composition, thermolabile acidic cannabinoids, low-abundance minor constituents, and stringent regulatory requirements for potency determination and contaminant screening. Conventional extraction protocols often struggle to satisfy these evolving technical and operational needs, driving a transition toward miniaturized sample-preparation strategies integrated with advanced chromatographic platforms. Aim: This narrative review evaluates contemporary miniaturized extraction techniques for cannabis and cannabinoid analysis and their coupling with modern analytical instrumentation, focusing on analytical performance, matrix applicability, sustainability, automation potential, and regulatory relevance. Results: Forty peer-reviewed studies published up to December 2025 were identified. Solid-phase microextraction (SPME), microextraction by packed sorbent (MEPS), dispersive liquid–liquid microextraction, fabric-phase sorptive extraction (FPSE), modified Quick, Easy, Cheap, Effective, Rugged and Safe (QuEChERS), and emerging sorbent-based approaches were identified as solutions to major analytical challenges, including preservation of acidic cannabinoids, lipid-rich matrices, trace-level detection, and high-throughput laboratory demands. MEPS and micro-solid-phase extraction (lSPE) showed suitability for biological fluids due to their enrichment capacity and automation compatibility, while SPME including headspace remained dominant for terpene and volatile profiling. When coupled to liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) or ultra-high-performance liquid chromatography–high-resolution mass spectrometry (UHPLC-HRMS), miniaturized workflows achieved limits of detection comparable to or superior to conventional protocols and aligned closely with green sample preparation principles. Challenges included fiber durability, sorbent selectivity, microscale reproducibility, and the absence of harmonized regulatory standards. Conclusion: Miniaturized extraction integrated with advanced chromatographic platforms represents a major advance in cannabis analytics, enabling greener, faster, and regulatory-fit workflows. Techniques such as MEPS, lSPE, and modified QuEChERS appear particularly suitable for routine implementation. Broader validation across product classes and formal standardization within pharmacopeial and ISO frameworks are required to ensure widespread adoption and regulatory acceptance.