Compound-specific isotope analysis (CSIA) is a powerful analytical technique that allows for the determination of stable isotope ratios within individual organic and inorganic compounds. This approach has become an essential tool in environmental, ecological, biogeochemical, and forensic sciences due to its ability to provide insights into complex processes at an unprecedented level of detail. 

The advent of CSIA techniques can be traced back to the latter half of the 20th century, following significant advancements in mass spectrometry and chromatography. Initially applied primarily in geochemistry and environmental science for understanding paleoclimate conditions, nutrient cycling, and tracing contaminant sources, its applications have rapidly expanded across diverse fields. Over the years, CSIA methodologies have matured and refined, allowing researchers to investigate complex processes with unprecedented precision. This evolution has paved the way for its use in areas such as ecology to study food webs and trophic interactions, forensics to identify drug sources or authenticate products, and even archaeology to explore ancient diets and trade routes. With the ability to discern subtle isotopic variations within specific compounds, CSIA has become a cornerstone in modern multidisciplinary research, providing critical information that often cannot be obtained through conventional bulk isotope analysis. Its historical development reflects a persistent pursuit of scientific innovation and an ever-growing need for detailed, compound-level understanding of natural and anthropogenic systems.

• 1950s-1970s: The groundwork for stable isotope analysis was laid by Harold C. Urey, who won the Nobel Prize in Chemistry in 1934 for his discovery of deuterium. The use of isotopes for tracing natural processes began with simple bulk measurements but soon progressed to more complex systems. The development of this technique was driven by advancements in analytical chemistry and mass spectrometry that allowed for greater precision and specificity in isotope ratio measurements. In the early stages, the concept of stable isotope fractionation was first established in natural processes such as photosynthesis and respiration, where researchers observed differences in the stable isotope ratios of carbon dioxide between plants and the atmosphere. This laid the groundwork for understanding how biological, chemical, and physical processes could alter the isotopic composition of specific molecules. The development of Gas Chromatography-Mass Spectrometry (GC-MS) technology has significantly propelled advancements in the field of compound-specific isotope analysis.

•  1970s-2000s:  The 1970s and 1980s were a critical period in the development of Compound-Specific Isotope Analysis (CSIA), representing a significant leap from bulk isotope analysis to the targeted examination of individual compounds. This era marked the establishment of CSIA as a scientific discipline with profound implications for environmental science, geochemistry, biology, and forensic studies.One of the pivotal advancements during this period was the groundbreaking work by scientists such as John M. Hayes, who pioneered the integration of Gas Chromatography (GC) with Isotope Ratio Mass Spectrometry (IRMS). This resulted in the creation of Gas Chromatography-Isotope Ratio Mass Spectrometry (GC-IRMS), which enabled researchers to measure the stable isotope ratios of specific volatile organic compounds (VOCs) for the first time with high precision and accuracy. The 1970s and 1980s saw substantial methodological improvements in sample preparation, compound extraction, and chromatographic separation techniques, allowing for more effective isolation of target compounds before isotopic measurement.

• 1990s-2000s: This breakthrough technology allowed CSIA to expand its applications dramatically. By the early 1990s, commercially available instruments enabled researchers to measure and compare stable isotope compositions of environmentally significant compounds across various spatial and temporal scales. The 1990s to the 2000s was a pivotal period for Compound-Specific Isotope Analysis (CSIA), witnessing substantial advancements in both methodology and application. During this era, CSIA matured from an emerging technique to a widely recognized analytical tool with profound implications across various scientific disciplines.The development of high-resolution Gas Chromatography-Isotope Ratio Mass Spectrometry (GC-IRMS) and its subsequent commercial availability revolutionized CSIA. This allowed researchers to measure stable isotope ratios at the compound level with greater accuracy and precision.

• 2000s-2020s: The 2000s and 2010s were marked by a surge in the advancement and application of Compound-Specific Isotope Analysis (CSIA) across multiple scientific disciplines. During this period, CSIA evolved from being a specialized technique to becoming a more routine and accessible tool for isotope-based research.The integration of high-performance liquid chromatography (HPLC) with isotope ratio mass spectrometry (IRMS) became more streamlined, leading to the widespread adoption of Liquid Chromatography-Isotope Ratio Mass Spectrometry (LC-IRMS). This allowed researchers to analyze non-volatile and semi-volatile compounds with greater ease and precision.

• The period from 2010 to 2020： in the history of Compound-Specific Isotope Analysis (CSIA) was characterized by remarkable advancements, broader applications, and a growing recognition of its importance in addressing complex environmental, biological, and forensic challenges. The sensitivity and precision of isotope ratio mass spectrometers improved significantly, allowing for the detection and measurement of isotopes in even trace amounts within individual compounds. This led to the analysis of minute samples and subtle isotopic signatures that were previously inaccessible. 

• High-Resolution Mass Spectrometry (HRMS): The integration of HRMS with CSIA techniques allowed researchers to achieve unprecedented detail in compound identification and isotopic measurements. This has been particularly useful in studying complex mixtures and elucidating transformation pathways. Real-Time Monitoring and In Situ Analysis: The advent of portable and miniaturized devices made it possible to perform CSIA in the field or under laboratory conditions without extensive sample preparation, enabling real-time monitoring of processes like biodegradation or chemical reactions.