Enabling heterogeneous catalysis to achieve carbon neutrality: Directional catalytic conversion of CO_(2) into carboxylic acids

The increase in anthropogenic carbon dioxide(CO_(2))emissions has exacerbated the deterioration of the global environment,which should be controlled to achieve carbon neutrality.Central to the core goal of achieving carbon neutrality is the utilization of CO_(2) under economic and sustainable conditions.Recently,the strong need for carbon neutrality has led to a proliferation of studies on the direct conversion of CO_(2) into carboxylic acids,which can effectively alleviate CO_(2) emissions and create high-value chemicals.The purpose of this review is to present the application prospects of carboxylic acids and the basic principles of CO_(2) conversion into carboxylic acids through photo-,electric-,and thermal catalysis.Special attention is focused on the regulation strategy of the activity of abundant catalysts at the molecular level,inspiring the preparation of high-performance catalysts.In addition,theoretical calculations,advanced technologies,and numerous typical examples are introduced to elaborate on the corresponding process and influencing factors of catalytic activity.Finally,challenges and prospects are provided for the future development of this field.It is hoped that this review will contribute to a deeper understanding of the conversion of CO_(2) into carboxylic acids and inspire more innovative breakthroughs.

Milk fat globule membrane supplementation protects againstβ-lactoglobul-ininduced food allergy in mice via upregulation of regulatory T cells and enhancement of intestinal barrier in a microbiota-derived short-chain fatty acids manner

Milk fat globule membrane(MFGM),which contains abundant glycoproteins and phospholipids,exerts beneficial effects on intestinal health and immunomodulation.The aim of this study was to evaluate the protective effects and possible underlying mechanisms of MFGM on cow’s milk allergy(CMA)in aβ-lactoglobulin(BLG)-induced allergic mice model.MFGM was supplemented to allergic mice induced by BLG at a dose of 400 mg/kg body weight.Results demonstrated that MFGM alleviated food allergy symptoms,decreased serum levels of lipopolysaccharide,pro-inflammatory cytokines,immunoglobulin(Ig)E,Ig G1,and Th2 cytokines including interleukin(IL)-4,while increased serum levels of Th1 cytokines including interferon-γand regulatory T cells(Tregs)cytokines including IL-10 and transforming growth factor-β.MFGM modulated gut microbiota and enhanced intestinal barrier of BLG-allergic mice,as evidenced by decreased relative abundance of Desulfobacterota,Rikenellaceae,Lachnospiraceae,and Desulfovibrionaceae,while increased relative abundance of Bacteroidetes,Lactobacillaceae and Muribaculaceae,and enhanced expressions of tight junction proteins including Occludin,Claudin-1 and zonula occludens-1.Furthermore,MFGM increased fecal short-chain fatty acids(SCFAs)levels,which elevated G protein-coupled receptor(GPR)43 and GPR109A expressions.The increased expressions of GPR43 and GPR109A induced CD103+dendritic cells accumulation and promoted Tregs differentiation in mesenteric lymph node to a certain extent.In summary,MFGM alleviated CMA in a BLG-induced allergic mice model through enhancing intestinal barrier and promoting Tregs differentiation,which may be correlated with SCFAs-mediated activation of GPRs.These findings suggest that MFGM may be useful as a promising functional ingredient against CMA.

Effects of forsythin extract in Forsythia leaves on intestinal microbiota and short-chain fatty acids in rats fed a high-fat diet

Forsythia suspensa,belonging to the deciduous shrubs of the Luteaceae family,a traditional Chinese medicine,has effects of alleviating swelling,clearing heat,detoxification and promoting blood circulation.The leaves of F.suspensa contain multiple chemical components and have a long history of use in folk medicines and health foods.The purpose of this study was to explore the effects of forsythin extract from F.suspensa leaves on intestinal microbiota and short-chain fatty acid(SCFA)content in rats with obesity induced by a high-fat diet.Forsythin extract in F.suspensa leaves increased the abundance of the intestinal microbiota,ameliorated intestinal microbiota disorders and inhibited the increase in total SCFA content in the intestinal tract in rats with obesity induced by a high-fat diet.These results suggested that forsythin extract in F.suspensa leaves may slow the development of obesity induced by a high-fat diet;thus,its active components and efficacy are worthy of further study.

Expression and clinical significance of short-chain fatty acids in patients with intrahepatic cholestasis of pregnancy

BACKGROUND Intrahepatic cholestasis of pregnancy(ICP)is a pregnancy-specific liver condition that typically arises in the middle and late stages of pregnancy.Short-chain fatty acids(SCFAs),prominent metabolites of the gut microbiota,have significant connections with various pregnancy complications,and some SCFAs hold potential for treating such complications.However,the metabolic profile of SCFAs in patients with ICP remains unclear.AIM To investigate the metabolic profiles and differences in SCFAs present in the maternal and cord blood of patients with ICP and determine the clinical significance of these findings.METHODS Maternal serum and cord blood samples were collected from both patients with ICP(ICP group)and normal pregnant women(NP group).Targeted metabolomics was used to assess the SCFA levels in these samples.RESULTS Significant differences in maternal SCFAs were observed between the ICP and NP groups.Most SCFAs exhibited a consistent declining trend in cord blood samples from the ICP group,mirroring the pattern seen in maternal serum.Correlation analysis revealed a positive correlation between maternal serum SCFAs and cord blood SCFAs[r(Pearson)=0.88,P=7.93e-95].In both maternal serum and cord blood,acetic and caproic acids were identified as key metabolites contributing to the differences in SCFAs between the two groups(variable importance for the projection>1).Receiver operating characteristic analysis demonstrated that multiple SCFAs in maternal blood have excellent diagnostic capabilities for ICP,with caproic acid exhibiting the highest diagnostic efficacy(area under the curve=0.97).CONCLUSION Compared with the NP group,significant alterations were observed in the SCFAs of maternal serum and cord blood in the ICP group,although they displayed distinct patterns of change.Furthermore,the SCFA levels in maternal serum and cord blood were significantly positively correlated.Notably,certain maternal serum SCFAs,specifically caproic and acetic acids,demonstrated excellent diagnostic efficiency for ICP.

Two New Phenolic Carboxylic Acid Esters from Opuntia vulgaris

Two new phenolic carboxylic acid esters n-butyl eucomate(1) and methyl eucomate (2) and six known compounds eucomic acid(3), 3-β-acetyl-taraxerol (4), friedelin(5),lupenone(6),methyl linoleate(7) and methyl oleate(8) were isolated from the stems of Opuntia vulgaris Mill(Cactaceae). Their structures were determined on the basis of spectral methods. Compounds 3,4,6,7,8 were isolated for the first time from this plant.

The role of gut microbiota and its metabolites short-chain fatty acids in food allergy

Emerging evidence indicated that the increase in food allergy(FA)over the past few decades was associated with the abnormal compositional and metabolic changes of gut microbiota.Gut microbiota played a vital role in maintaining the homeostasis of the immune system and the dysbiosis of gut microbiota promoted the occurrence of FA.Recent research suggested that short-chain fatty acids(SCFAs),the main metabolites derived from gut microbiota,contributed to FA protection.Herein,we provided a comprehensive review on the relationship between gut microbiota and FA.The multifaceted mechanisms underlymg beneficial effects of gut microbiota composition/metabolites on the regulation of diverse cellular pathways in intestinal epithelial cells,dendritic cells,innate lymphoid cells,T cells,B cells and mast cells in the immune system were discussed systematically.These findings emphasized the positive function of gut microbiota in FA and provided novel ideas for the treatment or prevention of FA in the future.

Unlocking a novel determinant of athletic performance:The role of the gut microbiota,short-chain fatty acids,and“biotics”in exercise

The gut microbiota refers to the collection of trillions of intestinal microorganisms that modulate central aspects of health and disease through influential effects on host physiology.Recently,a connection has been made between the gut microbiota and exercise.Initial investigations demonstrated the beneficial effects of exercise on the gut microbiota,with cross-sectional studies revealing positive correlations between exerciseassociated states,and healthy gut microbiota and exercise interventions showed post-intervention increases in the abundance of beneficial bacterial taxa.More recent investigations have focused on exploring the reverse relationship:the influence of the gut microbiota on exercise performance.Murine investigations have revealed that certain bacterial taxa may enhance endurance exercise performance by augmenting various aspects of lactate metabolism.Further,short-chain fatty acids—which modulate metabolism at various organ sites,including within skeletal muscle—have been shown to enhance endurance exercise capacity in mice.This review highlights what is currently known about the connection between the gut microbiota and exercise,with a particular focus on the ergogenic potential of the gut microbiota and how it may be leveraged to enhance endurance exercise performance.

Supplementing the early diet of broilers with soy protein concentrate can improve intestinal development and enhance short-chain fatty acid-producing microbes and short-chain fatty acids,especially butyric acid

Background:Research on nutrition in early-life commonly focuses on the maturation of the intestine because the intestinal system is crucial for ensuring continued growth.To explore the importance of early nutrition regulation in animals,soy protein concentrate(SPC)was added to the early diet of broilers to investigate its effects on amino acid digestibility,intestinal development,especially intestinal microorganisms,and broiler metabolites.A total of 192 oneday-old Arbor Acres(AA)male broilers were randomly assigned to two experimental treatments with 8 replicates of 12 birds.The control group was fed a basal diet(control),and the treatment group was fed a basal diet supplemented with 12%SPC(SPC12)during the first 10 d(starter phase).From d 11 to 21(grower phase)and d 22 to 42(finisher phase),a basal diet was fed to both treatment groups.Results:SPC reduced the pH value and acid-binding capacity of the starter diet(P<0.05,d 10);SPC in the early diet enhanced the gizzard weight(P<0.05,d 10 and d 42)and the ileum weight(P<0.05,d 10)and decreased the weight and length of the jejunum(P<0.05,d 10)and the relative length of the duodenum and jejunum(P<0.05,d 10).At the same time,SPC enhanced villus height(P<0.05,d 10)and muscle thickness in the jejunum and ileum(P<0.05,d 10)and increased the number of goblet cells in the duodenum(P<0.05,d 10).Meanwhile,SPC increased the Chao1 index and the ACE index(P<0.05,d 10)and altered the composition of caecal microflora at d 10.SPC also increased the relative abundance of Alistipes,Anaerotruncus,Erysipelatoclostridium,Intestinimonas and Flavonifractor bacteria(P<0.05,d 10).At the same time,the concentrations of caecal butyric acid and total short-chain fatty acids(SCFAs)were also increased in the SPC12 group(P<0.05,d 10).Conclusions:In summary,the results showed that supplementing the starter diet of broilers with SPC has a significant effect on the early development of the intestine and the microflora.

Supplementation with yak (Bos grunniens) bone collagen hydrolysate altered the structure of gut microbiota and elevated short-chain fatty acid production in mice

In this study, yak bone collagen hydrolysate(YBCH)was produced by mixed proteases and provided to standard-diet mice at a different dose(low dose(LD), medium dose(MD), and high dose(HD))to investigate its effects on the composition of gut microbiota and short-chain fatty acids(SCFA)production. It was found that YBCH was mainly composed of small molecular peptides whose molecular weight below 2 000 Da. Notably, supplementation with different doses of YBCH could significantly downregulate the ratio of Firmicutes to Bacteroidetes in the fecal microbiota. At the family level, the Lachnospiraceae abundance was significantly reduced in the YBCH gavage groups(mean reduction ratio 41.7 %, 35.2%, and 36.4% for LD, MD, and HD group, respectively). The predicted functions of gut microbes in the MD group were significantly increased at “lipid metabolism” and “glycan biosynthesis and metabolism”. Moreover, the SCFA production in the YBCH groups was elevated. Especially, the concentration of acetic acid, propionic acid, and butyric acid in the MD group was separately increased 79.7%, 89.2%, and 78.8% than that in the NC group. These results indicated that YBCH might be applied in the development of functional food for intestinal microecological regulation.

Cinnamic acid regulates the intestinal microbiome and short-chain fatty acids to treat slow transit constipation

BACKGROUND Slow transit constipation(STC)is a disorder with delayed colonic transit.Cinnamic acid(CA)is an organic acid in natural plants,such as Radix Scrophulariae(Xuan Shen),with low toxicity and biological activities to modulate the intestinal microbiome.AIM To explore the potential effects of CA on the intestinal microbiome and the primary endogenous metabolites-short-chain fatty acids(SCFAs)and evaluate the therapeutic effects of CA in STC.METHODS Loperamide was applied to induce STC in mice.The treatment effects of CA on STC mice were assessed from the 24 h defecations,fecal moisture and intestinal transit rate.The enteric neurotransmitters:5-hydroxytryptamine(5-HT)and vasoactive intestinal peptide(VIP)were determined by the enzyme-linked immunosorbent assay.Hematoxylin-eosin and Alcian blue and Periodic acid Schiff staining were used to evaluate intestinal mucosa's histopathological performance and secretory function.16S rDNA was employed to analyze the composition and abundance of the intestinal microbiome.The SCFAs in stool samples were quantitatively detected by gas chromatography-mass spectrometry.RESULTS CA ameliorated the symptoms of STC and treated STC effectively.CA ameliorated the infiltration of neutrophils and lymphocytes,increased the number of goblet cells and acidic mucus secretion of the mucosa.In addition,CA significantly increased the concentration of 5-HT and reduced VIP.CA significantly improved the diversity and abundance of the beneficial microbiome.Furthermore,the production of SCFAs[including acetic acid(AA),butyric acid(BA),propionic acid(PA)and valeric acid(VA)]was significantly promoted by CA.The changed abundance of Firmicutes,Akkermansia,Lachnoclostridium,Monoglobus,UCG.005,Paenalcaligenes,Psychrobacter and Acinetobacter were involved in the production of AA,BA,PA and VA.CONCLUSION CA could treat STC effectively by ameliorating the composition and abundance of the intestinal microbiome to regulate the production of SCFAs.

Sensitive Voltammetric Determination of Captopril Using a Carbon Paste Electrode Modified with Nano-TiO_2/Ferrocene Carboxylic Acid

A carbon paste electrode (CPE) modified with ferrocene carboxylic acid (FcCA) and TiO2 nanoparticles was constructed by incorporating TiO2 nanoparticles and ferrocene carboxylic acid into the carbon paste matrix. The electrochemical behavior of captopril (CAP) at the surface of the modified electrode was investigated using electroanalytical methods. The modified electrode showed excellent electrocatalytic activity for the oxidation of CAP in aqueous solutions at physiological pH values. Cyclic voltammetric curves showed that the oxidation of CAP at the surface of the modified electrode reduced its overpotential by more than 290 mV. The modified electrode was used for detecting captopril using cyclic voltammetry and square wave voltammetry techniques. A calibration curve in the range of 0.03 to 2400 μmol/L was obtained that had a detection limit of 0.0096 μmol/L (3?) under the optimized conditions. The modified electrode was successfully used for the determination of captopril in pharmaceutical and biological samples.

Sulfonated carbon catalyzed oxidation of aldehydes to carboxylic acids by hydrogen peroxide

Sulfonated carbon as a strong and stable solid acid catalyst exhibited excellent catalytic performance in various acid-catalyzed reactions. Here, sulfonated carbon, as catalyst for oxidation reaction, was prepared via the carbonization of starch followed by sulfonation with concentrated sulfuric acid. N2 physisorption, X-ray diffraction, Fourier transform infrared spectroscopy, X-ray fluorescence and acid-base titration were used to characterize the obtained materials. The catalytic activity of sulfonated carbon was studied in the oxidation of aldehydes to carboxylic acids using 30 wt% H2O2 as oxidant. This oxidation protocol works well for various aldehydes including aromatic and aliphatic aldehydes. The sulfonated carbon can be recycled for three times without obvious loss of activity.

Efficient Fixation of Carbon Dioxide by Electrolysis——Facile Synthesis of Useful Carboxylic Acids

Electrochemical fixation of atmospheric pressure of carbon dioxide to organic compounds is a useful and attractive method for synthesizing of various carboxylic acids. Electrochemical fixation of carbon dioxide, electrochemical carboxylation, organic halides, organic triflates, alkenes, aromatic compounds, and carbonyl compounds can readily occur in the presence of an atmospheric pressure of carbon dioxide to form the corresponding carboxylic acids with high yields, when a sacrificial anode such as magnesium or aluminum is used in the electrolysis. The electrochemical carboxylation of vinyl bromides was successfully applied for the synthesis of the precursor of nonsteroidal anti-inflammatory agents such as ibuprofen and naproxen. On the other hand, supercritical carbon dioxide （scCO2） has significant potential as an environmentally benign solvent in organic synthesis and it could be used both as a solvent and as a reagent in these electrochemical carboxylations by using a small amount of cosolvent.

Syntheses,Crystal Structures and Antibacterial Activities of 5-Chloro-3-methyl-1-phenyl-1H-pyrazole-4-carboxylic Acid and Its Copper(Ⅱ) Compound

The title compounds 5-chloro-3-methyl-1-phenyl-1H-pyrazole-4-carboxylic acid（C11H9Cl N2O2, HL）（1） and [Cu（L）2（H2O）]（2） were prepared and structurally characterized by elemental analysis, IR and single-crystal X-ray diffraction. Compound 1（C11H9Cl N2O2） crystallizes in the monoclinic system, space group P21/n with a = 7.249（3）, b = 20.515（10）, c = 7.249（3）,β= 96.30°, V = 1071.6（9） ？3, Z = 4, Mr = 236.65, Dc = 1.467 g/cm3, F（000） = 488, GOOF = 1.029, μ= 0.341 mm-1, the final R = 0.0736 and w R = 0.1966 for 1500 observed reflections with I 〉 2σ（I）. Compound 2（C22H18Cl2Cu N4O5） crystallizes in the monoclinic system, space group P21/c with a = 7.2931（6）, b = 24.548（2）, c = 13.2726（11）, β= 99.4040（10）°, V = 2344.2（3） ？3, Z = 4, Mr = 552.84, Dc = 1.566 g/cm3, F（000） = 1124, GOOF = 1.050, μ= 1.201 mm-1, the final R = 0.0376 and w R = 0.1000 for 3626 observed reflections with I 〉 2σ（I）. 1 and 2 are connected through hydrogen bonding interactions to generate 2D and 3D supramolecular structures, respectively. Moreover, the preliminary antibacterial activities of 1 and 2 against the gram positive bacteria（S. aureus, C. albicans and B. subtilis） and gram negative bacteria（E. coli and P. aeruginosa） have been tested by using the microdilution method, and the results indicate that 2 is more active than 1 against the tested bacteria.

Comparison of Carboxylic Acids in Some Crude Oils and Their Diesel Distillates and VGOs:Characterized by Negative-Ion Electrospray Ionization Fourier Transform Ion Cyclotron Resonance Mass Spectrometry (Negative-Ion ESI FT-ICR MS)

Three high-acidity crudes, Dar, SZ36-1, and QHD326, were separated through distillation into several fractions, including diesel distillates, and VGOs. Samples were characterized by negative-ion ESI FT-ICR MS. The O2 class species （petroleum carboxylic acids）, which have a close relationship with corrosion of equipment caused by high-acidity crudes, were put in the focus of attention and were discussed in this paper. Monocyclic, bicyclic, and tricyclic naphthenic acids are the main types of petroleum carboxylic acids in naphthenic-base crudes （SZ36-1 and QHD326）. But the main types of petroleum carboxylic acids in paraffinic-base crude （Dar） are aliphatic acids and monocyclic naphthenic acids. The O2 class species in SZ36-1 and QHD326 are distributed in a wider range and have bigger DBE value （double-bond equivalence value） and carbon number than Dar. Bicyclic naphthenic acids have the highest proportion among petroleum carboxylie acids in diesel distillates, but monocyclic and tricyclic naphthenic acids also occupy a high proportion. Particularly, aliphatic acids in the diesel distillate of Dar still have high proportion among petroleum carboxylic acids. The distribution of petroleum carboxylic acids in VGO is basically identical. The bicyclic naphthenic acids assume the first place （about 25 m%）, while the monocyclic and tricyclic naphthenic acids take the next place. The comparison of petroleum carboxylic acids in diesel distillates and VGOs has revealed that the molecules of carboxylic acids in VGOs are not only bigger but also more complicated.

Gut microbiota as a target in the bone health of livestock and poultry: roles of short-chain fatty acids

The regulation and maintenance of bone metabolic homeostasis are crucial for animal skeletal health.It has been established that structural alterations in the gut microbiota and ecological dysbiosis are closely associated with bone metabolic homeostasis.The gut microbiota and its metabolites,especially short-chain fatty acids(SCFAs),affect almost all organs,including the bone.n this process,SCFAs positively affect bone healing by acting directly on cells involved in bone repair after or by shaping appropriate anti-inflammatory and immunomodulatory responses:Addi-tionally,SCFAs have the potential to maintain bone health in livestock and poultry because of their various biological functions in regulating bone metabolism,including immune function,calcium absorption,osteogenesis and oste-olysis.This review primarily focuses on the role of sCFAs in the regulation of bone metabolism by gut microbiota and provides insight into studies related to bone health in livestock and poultry.

Reductive Conversion of Biomass-Derived Furancarboxylic Acids with Retention of Carboxylic Acid Moiety

Catalytic reduction systems of 2-furancarboxylic acid(FCA)and 2,5-furandicarboxylic acid(FDCA)with H 2 without reduction of the carboxyl groups are reviewed.FCA and FDCA are produced from furfural and 5-hydroxymethylfurfural which are important platform chemicals in biomass conversions.Furan ring hydrogenation to tetrahydrofuran-2-carboxylic acid(THFCA)and tetrahydrofuran-2,5-dicarboxylic acid(THFDCA)easily proceeds over Pd catalysts.Hydrogenolysis of one C–O bond in the furan ring produces 5-hydroxyvaleric acid(5-HVA)and 2-hydroxyadipic acid.2-Hydroxyvaleric acid is not produced in the reported systems.5-HVA can be produced as the lactone form(δ-valerolactone;DVL)or as the esters depending on the solvent.These reactions proceed over Pt catalysts with good yields(~70%)at optimized conditions.Hydrogenolysis of two C–O bonds in the furan ring produces valeric acid and adipic acid,the latter of which is a very important chemical in industry and its production from biomass is of high importance.Adipic acid from FDCA can be produced directly over Pt-MoO_(x) catalyst,indirectly via hydrogenation and hydrodeoxygenation as one-pot reaction using the combination of Pt and acid catalysts such as Pt/niobium oxide,or indirectly via two-step reaction composed of hydrogenation catalyzed by Pd and hydrodeoxygenation catalyzed by iodide ion in acidic conditions.Only the two-step method can give good yield of adipic acid at present.

Synthesis and Properties of Ternary Europium Complexes with Aromatic Carboxylic Acid and Nitrogen-Containing Heterocyclic Ligand

Seven ternary Eu （m） complexes were synthesized with aromatic carboxylic acid （benzoic acid, phenylacetic acid, phenylpropionic acid and cinnamic acid） as the first ligand and 1,10-phenanthro- line or 2,2＇-dipyridyl as the second ligand. The ternary Eu（ Ⅲ ） complexes were characterized by elemental analysis, IR and TG-DTG methods. In these complexes, the Eu （Ⅲ） ions are bonded to the oxygen atoms of carboxylate and the nitrogen atoms of neutral ligands. Four complexes whose second ligand is 1,10- phenanthrolin have fine thermal stability. Excitation and luminescence spectra of the tide complexes reveal that the fluorescence of the complexes in which 1,10- phenanthrolin as the second ligand are more intensive than those complexes in which 2, 2＇-dipyridyl as the second ligand. The order of the strongest emission peak of seven ternary complexes is： Eu（β-PPA）3phen 〉 Eu（BA）3phen 〉 Eu（PLA）3phen 〉 Eu（BA）3bipy 〉 Eu （ PEA）3bipy 〉 Eu （ CA ）3phen · H2O 〉 Eu （ CA ）3bipy （BA ： benzoic ; PEA ： phenylacetic ; β-PPA ：

Theoretic Simulation of Pr^(3+) and Nd^(3+) Complexes with αHydroxyl Carboxylic Acids

The potential energy difference of trivalent Pr/Nd complex ions with various α hydroxyl carboxylic acids were computed by molecular mechanics plus(MM +) model. Its relationships with the steric hindrance of the coordinating lignads and with the separation factor of Pr/Nd were discussed. It is found that the MM + model can be used for selecting and designing ligand as effective eluant, with which Pr 3+ and Nd 3+ can be separated by ion exchange chromatography.

Determination of Clopidogrel Carboxylic Acid in Human Plasma by LC-MS/MS

Background: Clopidogrel, is a thienopyridine derivative labeled for use to prevent thrombosis after coronary artery stenting. Pharmacokinetics of clopidogrel is studied indirectly by quantification of carboxylic acid which is a major metabolite of Clopidogrel. Objective: The aim of this work is to develop and validate a rapid, simple and sensitive LC/MS/MS assay method for the determination of Clopidogrel carboxylic acid in human plasma using Clopidogrel-D4-carboxylic acid as internal standard. Methods: Analytes was extracted from 200 μl of plasma by a simple liquid-liquid extraction using diethyl ether – n-hexane (80:20, v/v). The chromatographic separations were achieved on a C18 column using Methanol, de-ionized water and formic acid as a mobile phase at flow rate of 0.5 ml/minute. Analysis was monitored by multiple reactions monitoring mode based on m/z transition of 308.10→113 for Clopidogrel carboxylic acid and 312.10→129 for internal standard. Result: The method had a total run time of about 4 minutes. The lower limit of quantification (LLOQ) was 25 ng/ml showing good linearity over the working range of 25 – 3000 ng/ml (r ≥ 0.999). The intra- and inter day accuracies were 90% - 98% and 92.138% - 96.889% respectively (deviation within acceptable range ≤ 10%).Conclusion: It was shown that this method is suitable for pharmacokinetic study following oral administration of Clopidogrel and can be successfully applied to the therapeutic drug monitoring of Clopidogrel in Clopidogrel-treated patients.