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<p>Tramadol, a widely prescribed synthetic opioid analgesic, presents distinctive analytical challenges due to its diverse formulations, active metabolites, stereochemical complexity, and growing potential for abuse. Accurate detection and quantification in pharmaceutical products, biological matrices, and forensic samples are crucial for ensuring quality control, therapeutic monitoring, and postmortem toxicological evaluation. This review critically examines the evolution of analytical methodologies for tramadol—focusing on innovations in sample preparation, detection strategies, and emerging sensor technologies relevant to pharmaceutical, clinical, and forensic domains. Analytical research on tramadol has advanced substantially over the past decade, driven by the need for sensitive, selective, and rapid analytical tools. Classical extraction techniques such as liquid–liquid extraction and the Stas–Otto method have been progressively replaced or enhanced by modern approaches, including solid-phase extraction (SPE), magnetic SPE, molecularly imprinted polymer microextraction, dispersive liquid–liquid microextraction, QuEChERS, and sol–gel-based extractions. These methods improve analyte recovery, selectivity, and matrix cleanup, thereby increasing detection accuracy in complex biological matrices. In terms of instrumental analysis, ultraviolet–visible spectrophotometry and high-performance liquid chromatography (HPLC) remain routinely applied, while advanced methods such as gas chromatography–mass spectrometry (GC–MS), liquid chromatography–tandem mass spectrometry (LC–MS/MS), and ultra-high-performance liquid chromatography (UHPLC) offer superior sensitivity, specificity, and non-interference from matrices. Cutting-edge innovations, including nanomaterial-based electrochemical sensors, molecularly imprinted polymers, and microfluidic detection platforms, have emerged as promising tools for rapid, on-site, and eco-friendly tramadol screening. Overall, analytical approaches to tramadol are shifting toward highly sensitive, miniaturized, and integrated platforms. The combination of advanced extraction procedures with state-of-the-art chromatographic, spectrometric, and sensor-based technologies ensures robust and cost-effective quantification across pharmaceutical, clinical, and forensic contexts. Future directions should emphasize sustainable, automated, and data-driven analytical systems to enhance throughput and reliability in tramadol determination.</p> Graphical Abstract <p></p>

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Tramadol in forensic and analytical toxicology: current advances and future perspectives—a review

  • 期刊论文

  • 发表日期：

    2026年3月14日

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  • Harrish Fernando,
  • Sachil Kumar,
  • S. Achiraman,
  • ElKhatim H. Abdelgadir,
  • Tulsidas R. Baggi

摘要

Tramadol, a widely prescribed synthetic opioid analgesic, presents distinctive analytical challenges due to its diverse formulations, active metabolites, stereochemical complexity, and growing potential for abuse. Accurate detection and quantification in pharmaceutical products, biological matrices, and forensic samples are crucial for ensuring quality control, therapeutic monitoring, and postmortem toxicological evaluation. This review critically examines the evolution of analytical methodologies for tramadol—focusing on innovations in sample preparation, detection strategies, and emerging sensor technologies relevant to pharmaceutical, clinical, and forensic domains. Analytical research on tramadol has advanced substantially over the past decade, driven by the need for sensitive, selective, and rapid analytical tools. Classical extraction techniques such as liquid–liquid extraction and the Stas–Otto method have been progressively replaced or enhanced by modern approaches, including solid-phase extraction (SPE), magnetic SPE, molecularly imprinted polymer microextraction, dispersive liquid–liquid microextraction, QuEChERS, and sol–gel-based extractions. These methods improve analyte recovery, selectivity, and matrix cleanup, thereby increasing detection accuracy in complex biological matrices. In terms of instrumental analysis, ultraviolet–visible spectrophotometry and high-performance liquid chromatography (HPLC) remain routinely applied, while advanced methods such as gas chromatography–mass spectrometry (GC–MS), liquid chromatography–tandem mass spectrometry (LC–MS/MS), and ultra-high-performance liquid chromatography (UHPLC) offer superior sensitivity, specificity, and non-interference from matrices. Cutting-edge innovations, including nanomaterial-based electrochemical sensors, molecularly imprinted polymers, and microfluidic detection platforms, have emerged as promising tools for rapid, on-site, and eco-friendly tramadol screening. Overall, analytical approaches to tramadol are shifting toward highly sensitive, miniaturized, and integrated platforms. The combination of advanced extraction procedures with state-of-the-art chromatographic, spectrometric, and sensor-based technologies ensures robust and cost-effective quantification across pharmaceutical, clinical, and forensic contexts. Future directions should emphasize sustainable, automated, and data-driven analytical systems to enhance throughput and reliability in tramadol determination.

Graphical Abstract