1. Introduction

Suk-Saiyasna is a traditional Thai medicine recipe containing 12 herbal ingredients in specific proportions: camphor one part; Azadirachta indica A. Juss. leaves—two parts; Kleinhovia hospita L. root—three parts; Cinnamomum bejolghota (Buch.-Ham.) Sweet bark—four parts; Nigella sativa L. seeds—five parts; Aucklandia lappa (Decne.) Decne. root—six parts; Myristica fragrans Houtt. fruit—seven parts; Mesua ferrea L. flowers—eight parts; Piper nigrum L. fruit—nine parts; Zingiber officinale Roscoe rhizome—ten parts; Piper retrofractum Vahl. fruit—eleven parts; and Cannabis sativa L. leaves—twelve parts (12 out of a total of 78 parts, equivalent to 15.38%). It is used as a multipurpose remedy, including as a sedative [1]. Recent studies suggest that a related herbal remedy may enhance the effects of γ-aminobutyric acid type A (GABAA) receptor-targeting drugs, potentially influencing sleep and sedation [2]. The growing interest in cannabinoids like Δ9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD) for therapeutic use has led to challenges in ensuring safety, quality, and regulatory compliance of cannabis-derived products, particularly in accurately measuring Δ9-THC and CBD concentrations across different formulations [3,4]. In accordance with the Thailand Narcotics Act 2022, which came into effect on 9 June 2022, specific components of the cannabis plant have been reclassified and are no longer considered Category 5 narcotics. These components comprise the bark, stems, fibers, branches, roots, and leaves devoid of flowers or buds. Moreover, any extracts containing Δ9-THC are required to have a concentration not exceeding 0.2% by weight [5].

The extraction of Δ9-THC from cannabis involves various methods, each with its own advantages and limitations. The main extraction techniques discussed are the following: (1) Solvent extraction: Uses organic solvents like ethanol, butane, or hexane. Ethanol is noted for its efficiency and safety [6]. (2) Supercritical fluid extraction (SFE): Primarily uses supercritical CO₂, allowing selective extraction of cannabinoids while minimizing undesirable compounds [7,8,9]. (3) Soxhlet extraction: A traditional method known for thoroughness but criticized for long extraction times and high solvent use [10]. (4) Microwave-assisted extraction (MAE): Uses microwave energy to enhance extraction, reducing time and increasing yields [11]. (5) Pressurized hot water extraction (PHWE): An environmentally friendly method using high-temperature, high-pressure water [12]. Each method affects the yield, purity, extraction time, and solvent usage differently. The choice of method depends on the specific requirements of the extraction process and the intended use of the final product.

The Hansen Solubility Parameter (HSP) framework offers a sophisticated approach to understanding compound solubility, particularly in herbal extraction contexts. Developed by Charles Hansen, HSPs decompose a substance’s cohesive energy density into three components: dispersion force (δd), polar force (δp), and hydrogen bonding (δh) parameters [13,14]. This tripartite division enables a nuanced comprehension of solvent–phytochemical interactions, crucial for optimizing extraction processes. The total Hansen Solubility Parameter (δt) is calculated as δt = √(δd² + δp² + δh²). This calculation facilitates the assessment of solvent efficacy in extracting specific compounds from plant materials [15]. Solvents that possess HSP values close to those of the target compounds generally result in higher extraction efficiencies, thereby reducing the reliance on empirical trial-and-error methods [16]. In herbal extraction, HSPs guide solvent selection to maximize desired phytochemical recovery while minimizing unwanted substance extraction. This approach aligns with green chemistry principles, promoting environmentally friendly solvents and reducing waste [17]. The Hansen Solubility Parameters provide a valuable tool for optimizing herbal extraction processes. By facilitating the selection of appropriate solvents based on their interaction with target phytochemicals, HSPs can enhance extraction efficiency, reduce environmental impact, and improve the overall quality of herbal products.

Group contribution methods (GCMs) and Hansen Solubility Parameters (HSPs) are essential for understanding solubility phenomena in various materials. GCMs are computational techniques used to estimate the HSPs of compounds based on their molecular structures. The fundamental principle of GCMs involves the decomposition of a molecule into its constituent functional groups, each of which is assigned a specific contribution to the overall property of interest. This methodology allows for the estimation of interaction parameters and thermodynamic properties using a limited set of empirical data, which is particularly advantageous in the context of complex mixtures and reactions [18,19].

In 1987, the United Nations Office on Drugs and Crime (UNODC) published the first manual on recommended methods for testing cannabis (ST/NAR/8), which was revised in 2009 and most recently updated in 2022. The UNODC recommended various analytical techniques and methodologies for the identification and analysis of cannabinoids in cannabis products. These techniques include simple color tests, thin-layer chromatography (TLC), gas chromatography–flame ionization detection (GC-FID), gas chromatography–mass spectrometry (GC-MS), liquid chromatography (LC), and liquid chromatography–mass spectrometry (LC-MS or LC-MS/MS), as well as combinations of these methods [20]. Furthermore, a novel methodology utilizing high-performance liquid chromatography with ultraviolet detection (HPLC-UV) has been developed, demonstrating success in analyzing cannabinoids within cannabis products [21].

Liquid chromatography–tandem mass spectrometry (LC-MS/MS) has become a crucial analytical tool in herbal medicine due to its ability to simultaneously identify and quantify multiple components in complex herbal samples [22,23]. Recent studies have demonstrated its effectiveness in analyzing traditional herbal formulas, detecting adulterants, and ensuring quality control [24]. LC-MS/MS can analyze complex herbal matrices, integrate with other analytical techniques, and facilitate rapid identification of compounds through automated dereplication processes [25]. As the herbal product market grows, LC-MS/MS plays an indispensable role in ensuring the safety, efficacy, and quality of these products. The technique’s versatility and comprehensive analytical capabilities make it essential for regulatory compliance and consumer safety in the field of herbal medicine.

In this study, we conducted a comprehensive quantitative analysis of Δ9-THC and CBD in commercial herbal remedies using UHPLC-MS/MS to address the separation issues associated with HPLC-UV. Unlike traditional extraction methods, which often involve the use of organic solvents with varying degrees of efficiency and reproducibility, we propose a novel approach based on Hansen Solubility Parameters (HSPs) for sample extraction. HSPs offer a systematic framework for predicting the solubility behavior of compounds in different solvents, thereby enabling the selection of optimal extraction conditions for cannabinoids with enhanced accuracy and reproducibility. Our methodology not only facilitates the efficient extraction of Δ9-THC and CBD from complex herbal matrices but also addresses critical concerns related to regulatory compliance. By employing HSP-based extraction, we aim to ensure consistency in cannabinoid quantification across different samples. These methodologies not only enhance extraction efficiency and yield but also promote the standardization of protocols, which is essential for obtaining reliable and reproducible results in cannabinoid research and its applications.