This review highlights the current state of knowledge in the development of GC × GC-MS for the analysis of clinical metabolites. Selected applications are described as well as our perspectives on current challenges and potential future directions.
Background: Aquilaria malaccensis Lam. is one of the very few lign-aloes trees that can produce highly valuable resin-impregnated heartwood, commonly known as agarwood. Aim: This study aimed to determine the chemical profile of A. malaccensis essential oil and describe its antiproliferative effects against the HeLa cervical cancer cell line for the first time. Method: The essential oils hydro-distilled from agarwood were characterised using GC−MS with the aid of spectral deconvolution. The antiproliferative effects were evaluated via the MTT assay. Result: A total of 143 metabolites were tentatively identified in two different grades of essential oils, which accounted for 56.80% and 78.19% of the total ion counts, respectively. These metabolites were distributed over the chemical families of monoterpenes, sesquiterpenes, cyclic hydrocarbons, and others. The essential oils exhibited antiproliferative activities, with IC50 values of 79.42 and 128.77 μg/mL, respectively. Conclusion: The results have suggested the chemical differences in secondary compounds to be the main factor contributing to the decrease in cell viability. Further investigations are warranted to understand its mechanisms of action and its potential use in cervical cancer treatment.
Over the last decades, comprehensive two-dimensional gas chromatography (GC×GC) has emerged as a significant separation tool for high-resolution analysis of disease-associated metabolites and pharmaceutically relevant molecules. This review highlights recent advances of GC×GC with different detection modalities for drug discovery and analysis, which ideally improve the screening and identification of disease biomarkers, as well as monitoring of therapeutic responses to treatment in complex biological matrixes. Selected recent GC×GC applications that focus on such biomarkers and metabolite profiling of the effects of drug administration are covered. In particular, the technical overview of recent GC×GC implementation with hyphenation to the key mass spectrometry (MS) technologies that provide the benefit of enhanced separation dimension analysis with MS domain differentiation is discussed. We conclude by highlighting the challenges in GC×GC for drug discovery and development with perspectives on future trends.
The essential oil derived from Citrus plants has long been used for medicinal purposes, due to its broad spectrum of therapeutic characteristics. To date, approximately 162 Citrus species have been identified, and many investigational studies have been conducted to explore the pharmacological potential of Citrus spp. oils. This study investigated the volatile constituents of essential oil distilled from the leaves of C. hystrix, C. limon, C. pyriformis, and C. microcarpa, using gas chromatography-quadrupole mass spectrometry. A total of 80 secondary compounds were tentatively identified, representing 84.88-97.99% of the total ion count and mainly comprising monoterpene (5.20-76.15%) and sesquiterpene (1.36-27.14%) hydrocarbons, oxygenated monoterpenes (3.91-89.52%) and sesquiterpenes (0.21-38.87%), and other minor chemical classes (0.10-0.52%). In particular, 27 compounds (1.19-39.06%) were detected across all Citrus species. Principal component analysis of the identified phytoconstituents and their relative quantities enabled differentiation of the Citrus leaf oils according to their species, with the loading variables contributing to these metabolic differences being identified. The Citrus leaf oils were tested for their antioxidant and antiproliferative activities using 2,2-diphenyl-1-picryl-hydrazylhydrate (DPPH) and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays. The results indicated that C. limon displayed the highest DPPH radical scavenging ability (IC50 value of 29.14 ± 1.97 mg/mL), while C. hystrix exhibited the lowest activity (IC50 value of 279.03 ± 10.37 mg/mL). On the other hand, all the Citrus oils exhibit potent antiproliferative activities against the HeLa cervical cancer cell line, with IC50 values of 11.66 μg/mL (C. limon), 20.41 μg/mL (C. microcarpa), 25.91 μg/mL (C. hystrix), and 87.17 μg/mL (C. pyriformis).
This study evaluates the applicability of enantioselective gas chromatography (eGC) and enantioselective comprehensive two-dimensional gas chromatography (eGC×GC) coupled with flame ionization detection for the stereospecific analysis of designated chiral monoterpenes within essential oils distilled from the leaves of Citrus hystrix (CH), C. limon (CL), C. pyriformis (CP), and C. microcarpa (CM). A cryogen-free solid-state modulator with a combination of enantioselective first-dimension and polar second-dimension column arrangements was used to resolve potential interferences in Citrus spp. leaf oils that can complicate the accurate determination of enantiomeric compositions. Interestingly, considerable variations were observed for the enantiomeric fractions (EFs) of the chiral terpenes. (+)-limonene was identified as the predominant enantiomer (60.3–98.9%) in all Citrus oils, (+)-linalool was the major enantiomer in CM (95.9%), (−)-terpenin-4-ol was the major isomer in CM (66.4%) and CP (61.1%), (−)-α-pinene was the dominant antipode in CL (55.5%) and CM (92.1%). CH contained (−)-citronellal (100%) as the pure enantiomer, while CL and CP have lower proportions (9.0–34.6%), and citronellal is absent in CM. The obtained enantiomeric compositions were compared and discussed with results from eGC using the same enantioselective column. To our knowledge, this work encapsulates the first report that details the EFs of these chiral monoterpenes in Citrus spp. leaf oil.
This study evaluates the volatile metabolic constituents and anticancer potential of essential oils distilled from the rhizomes of four Malaysian Zingiber officinale Roscoe (Zingiberaceae family) varieties (Bentong (BE), Cameron Highlands (CH), Sabah (SA), and Bara (BA)). The ginger essential oils were analyzed by gas chromatography coupled with quadrupole mass spectrometry (GC qMS). A total of 58 secondary compounds were tentatively identified, representing 82.6-87.4% of the total ion count. These metabolites comprise mainly of monoterpene hydrocarbons (19.7-25.5%), oxygenated monoterpenes (23.6-33.7%), sesquiterpene hydrocarbons (21.3-35.6%), oxygenated sesquiterpenes (1.5-3.9%), and other minor classes of compounds (0.7-2.7%). Principal component analysis (PCA) enabled differentiation of the analyzed ginger essential oils according to their varieties, with respect to their metabolites and relative quantities. The antiproliferative activity against the HeLa cervical cancer cell line was investigated via the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The oils were found to exhibit strong antiproliferative activities with IC50 values of 23.8, 35.3, 41.3, and 42.5 μg/mL for BA, BE, SA, and CH, respectively. These findings suggest that the differences among the secondary metabolites and their abundance in different varieties of Z. officinale essential oils appear to be related to their antiproliferative potential. The strong antiproliferative effects of these oils signified their potential in the prevention and chemotherapy of cervical carcinoma treatment.
Background: The application of enantioselective capillary electrophoresis approach for the assessment of the enantiomeric purity of chiral molecules is receiving increased attention. Abscisic acid is one of the chiral sesquiterpenic plant growth regulators that regulate various ecological and physiological roles in higher plants. Enantiomeric determination of ABA is of great concern because of the different biological activity of its enantiomers. Materials and Methods: In this study, we investigated the enantioseparation selectivity of ABA by incorporating native β-cyclodextrins (β-CD) and its derivatives as chiral modifiers in the background electrolyte of an enantioselective capillary zone electrophoresis system. Electrophoretic aspects that affect the enantiomeric separation, such as pH, types of β-CD and its concentration, applied voltage, injection pressure and time, were studied and optimised. Results and Discussions: An enhancement in enantioseparation was achieved in a bare fused-silica capillary (64.5 cm × 50 mm i.d.) using a background electrolyte solution consisting of (2-hydroxypropyl)- β-CD (80 mM) solubilised in 100 mM phosphate buffer adjusted to pH 5.9 with NaOH, operated under normal polarity mode (25 kV) at 25°C, and using hydrodynamic injection (75 mbar for 10s). Relative standard deviations of (intra- and inter-day) ≤ 3.23% and ≤ 1.39% for migration times and enantiomeric fractions (EF) were achieved using the proposed method. Conclusion: The proposed chiral capillary electrophoretic method offers advantages in terms of enantioselectivity and analysis times, which can serve as a reliable platform for the stereoisomeric analysis of ABA.
'/%3e%3cuse xlink:href='%23a' transform='translate(0 -400)'/%3e%3cuse xlink:href='%23a' transform='translate(0 -600)'/%3e%3cuse xlink:href='%23a' transform='translate(0 -800)'/%3e%3cuse xlink:href='%23a' transform='translate(0 -1000)'/%3e%3cuse xlink:href='%23a' transform='translate(0 -1200)'/%3e%3cpath d='M0 0h1400v800H0z' style='fill:%23010066'/%3e%3cpath d='M576 100c-166.146 0-301 134.406-301 300s134.854 300 301 300c60.027 0 115.955-17.564 162.927-47.783-27.353 9.44-56.71 14.602-87.271 14.602-147.327 0-266.897-119.172-266.897-266.01 0-146.837 119.57-266.01 266.897-266.01 32.558 0 63.746 5.815 92.602 16.468C696.217 118.91 638.305 100 576 100z' style='fill:%23fc0'/%3e%3cpath d='m914.286 471.429-99.538-53.25 29.43 108.982-66.575-91.165-20.77 110.96-20.428-111.024-66.857 90.96L699.314 418l-99.701 52.943 74.065-85.192-112.8 4.441 103.694-44.62-103.555-44.94L673.8 305.42 600 220l99.538 53.25-29.43-108.982 66.575 91.165 20.77-110.96 20.428 111.023 66.857-90.959L814.97 273.43l99.702-52.944-74.065 85.193 112.8-4.441-103.694 44.62 103.555 44.94-112.785-4.79z' style='fill:%23fc0' transform='matrix(1.2738 0 0 1.2423 -89.443 -29.478)'/%3e%3c/svg%3e)
'/%3e%3c/defs%3e%3cpath fill='%23012169' d='M0 0h10080v5040H0z'/%3e%3cpath stroke='%23fff' stroke-width='.6' d='m0 0 6 3m0-3L0 3' clip-path='url(%23b)' transform='scale(840)'/%3e%3cpath stroke='%23e4002b' stroke-width='.4' d='m0 0 6 3m0-3L0 3' clip-path='url(%23c)' transform='scale(840)'/%3e%3cpath stroke='%23fff' stroke-width='840' d='M2520 0v2520M0 1260h5040'/%3e%3cpath stroke='%23e4002b' stroke-width='504' d='M2520 0v2520M0 1260h5040'/%3e%3cg fill='%23fff'%3e%3cuse xlink:href='%23d' x='2520' y='3780'/%3e%3cuse xlink:href='%23a' x='7560' y='4200'/%3e%3cuse xlink:href='%23a' x='6300' y='2205'/%3e%3cuse xlink:href='%23a' x='7560' y='840'/%3e%3cuse xlink:href='%23a' x='8680' y='1869'/%3e%3cuse xlink:href='%23e' x='8064' y='2730'/%3e%3c/g%3e%3c/svg%3e)
'%3e%3cpath fill='%23012169' d='M0 0v30h60V0z'/%3e%3cpath stroke='%23fff' stroke-width='6' d='m0 0 60 30m0-30L0 30'/%3e%3cpath stroke='%23C8102E' stroke-width='4' d='m0 0 60 30m0-30L0 30' clip-path='url(%23b)'/%3e%3cpath stroke='%23fff' stroke-width='10' d='M30 0v30M0 15h60'/%3e%3cpath stroke='%23C8102E' stroke-width='6' d='M30 0v30M0 15h60'/%3e%3c/g%3e%3c/svg%3e)