Development of a Carbon Paste Electrode Modified with Reduced Graphene Oxide and an Imidazole Derivative for Simultaneous Determination of Biological Species of N‐acetyl‐L‐cysteine,Uric Acid and Dopamine

In this work, the modified carbon paste electrode (CPE) with an imidazole derivative 2‐(2,3 dihydroxy phenyl) 4‐methyl benzimidazole (DHPMB) and reduced graphene oxide (RGO) was used as an electrochemical sensor for electrocatalytic oxidation of N‐acetyl‐L‐cysteine (NAC). The electrocatalytic oxidation of N‐acetyl‐L‐cysteine on the modified electrode surface was then investigated, indicating a reduction in oxidative over voltage and an intensive increase in the current of analyte. The scan rate potential, the percentages of DHPMB and RGO, and the pH solution were optimized. Under the optimum conditions, some parameters such as the electron transfer coefficient (α) between electrode and modifier, and the electron transfer rate constant) k_s) in a 0.1 M phosphate buffer solution (pH=7.0) were obtained by cyclic voltammetry method. The diffusion coefficient of species (D) 3.96×10^?5 cm² s^?1 was calculated by chronoamperometeric technique and the Tafel plot was used to calculate α (0.46) for N‐ acetyl‐L‐cysteine. Also, by using differential pulse voltammetric (DPV) technique, two linear dynamic ranges of 2–18 µM and 18–1000 µM with the detection limit of 61.0 nM for N‐acetyl‐L‐cysteine (NAC) were achieved. In the co‐existence system of N‐acetyl‐L‐cysteine (NAC), uric acid (UA) and dopamine (DA), the linear response ranges for NAC, UA, and DA are 6.0–400.0 µM, 5.0–50.0 µM and 2.0–20.0 µM, respectively and the detection limits based on (C=3s_b/m) are 0.067 µM, 0.246 µM and 0.136 µM, respectively. The obtained results indicated that DHPMB/RGO/CPE is applicable to separate NAC, uric acid (UA) and dopamine (DA) oxidative peaks, simultaneously. For analytic performance, the mentioned modified electrode was used for determination of NAC in the drug samples with acceptable results, and the simultaneous determination of NAC, UA and DA oxidative peaks was investigated in the serum solutions, too.     

A simple and sensitive assay for eflornithine quantification in rat brain using pre‐column derivatization and UPLC‐MS/MS detection

Eflornithine (α‐difluoromethylornithine) has been used to treat second‐stage (or meningoencephalitic‐stage) human African trypanosomiasis and currently is under clinical development for cancer prevention. In this study, a new ultraperformance liquid chromatography–tandem mass spectrometry (UPLC‐MS/MS)‐based assay was developed and validated for the quantification of eflornithine in rat brain. To improve chromatographic retention and MS detection, eflornithine was derivatized with 6‐aminoquinolyl‐N‐hydroxysuccinimidyl carbamate for 5 min at room temperature prior to injection. Derivatized eflornithine was separated on a reverse‐phase C₁₈ UPLC column with a 6‐min gradient; elution occurred at approximately 1.5 min. Prior to derivatization, eflornithine was reproducibly extracted from rat brain homogenate by methanol protein precipitation (~70% recovery). Derivatized eflornithine was stable in the autosampler (6 °C) for at least 24 h. This new assay had acceptable intra‐ and interday accuracy and precision over a wide dynamic range (5000‐fold) and excellent sensitivity with a lower limit of quantification of 0.1 µm (18 ng/mL) using only 10 μL of rat brain homogenate. The validated eflornithine assay was applied successfully to determine eflornithine distribution in different regions of rat brain in an in situ rat brain perfusion study. Copyright © 2014 John Wiley & Sons, Ltd.     

Simultaneous quantification and rat pharmacokinetics of formononetin‐7‐O‐β‐d‐glucoside and its metabolite formononetin by high‐performance liquid chromatography–tandem mass spectrometry

Formononetin‐7‐O‐β‐d ‐glucoside has been proved to have significant anti‐inflammatory effect. To evaluate its rat pharmacokinetics, a rapid, sensitive, and specific liquid chromatography–tandem mass spectrometry method has been developed and validated for the quantification of formononetin‐7‐O‐β‐d ‐glucoside and its main metabolite formononetin in rat plasma. Samples were pretreated using a simple protein precipitation and the chromatographic separation was performed on a C₁₈ column by a gradient elution using a mobile phase consisting of water and acetonitrile both containing 0.1% formic acid. Both analytes were detected using a tandem mass spectrometer in positive multiple reaction monitoring mode. The assay showed wide linear dynamic ranges of both 0.10–100 ng/mL, with acceptable intra‐ and inter‐batch accuracy and precision. The lower limits of quantification were both 0.10 ng/mL using 50 μL of rat plasma for two analytes. The method has been successfully used to investigate the oral pharmacokinetic profiles of both analytes in rats. After oral administration of formononetin‐7‐O‐β‐d ‐glucoside at the dose of 50 mg/kg, it was rapidly absorbed in vivo and metabolized to its metabolite formononetin. The plasma concentration‐time profiles both showed double‐peak phenomena, which would be attributed to the strong enterohepatic circulation of formononetin‐7‐O‐β‐d ‐glucoside.     

A liquid chromatography/tandem mass spectrometry method for detecting UGT‐mediated bioactivation of drugs as their N‐acetylcysteine adducts in human liver microsomes

The detection of the reactive metabolites of drugs has recently been gaining increasing importance. In vitro trapping studies using trapping agents such as glutathione are usually conducted for the detection of reactive metabolites, especially those of cytochrome P450‐mediated metabolism. In order to detect the UDP‐glucuronosyltransferase (UGT)‐mediated bioactivation of drugs, an in vitro trapping method using N‐acetylcysteine (NAC) as a trapping agent followed by liquid chromatography/tandem mass spectrometry (LC/MS/MS) was developed in this study. After the test compounds (diclofenac and ketoprofen) had been incubated in human liver microsomes with uridine diphosphoglucuronic acid (UDPGA) and NAC, the NAC adducts formed through their acyl glucuronides were analyzed using LC/MS/MS with electrospray ionization (ESI). The NAC adduct showed a mass shift of 145 units as compared to its parent, and the characteristic ion fragmentations reflected the parent. This is a concise and high‐throughput method for evaluating reactive metabolites by UGT‐mediated bioactivation. Copyright © 2009 John Wiley & Sons, Ltd.     

Simultaneous estimation of levodopa,carbidopa and 3‐oxymethyldopa in rat plasma using HPLC‐ECD

The aim of study was to develop a suitable analytical method for simultaneous estimation of levodopa, carbidopa and 3‐O‐methyl dopa in rat plasma. Chromatographic separation of plasma samples was achieved using a reverse‐phase C₁₈ column. The mobile phase used consisted of a mixture of methanol and phosphate buffer (10 mM , pH 3.50) in the ratio of 90:10 v/v. All analytes were estimated by electrochemical detection at +800 mV. The developed method has been validated as per the standard guidelines. Precision study results were found to be satisfactory, with percentage relative standard deviation for repeatability and intermediate precision <3.96 and 6.56%, respectively, for all analytes detected in rat plasma. The developed method in rat plasma was found to be simple, rapid, accurate, precise and specific. The proposed method has been successfully applied for analysis of rat plasma samples obtained during an oral pharmacokinetic study of sustained release pellets of levodopa and carbidopa in rats. Copyright © 2016 John Wiley & Sons, Ltd.     

An N‐Acetyl Cysteine Ruthenium Tricarbonyl Conjugate Enables Simultaneous Release of CO and Ablation of Reactive Oxygen Species

We have designed and synthesised a [Ru(CO)₃Cl₂(NAC)] pro‐drug that features an N‐acetyl cysteine (NAC) ligand. This NAC carbon monoxide releasing molecule (CORM) conjugate is able to simultaneously release biologically active CO and to ablate the concurrent formation of reactive oxygen species (ROS). Complexes of the general formulae [Ru(CO)₃(L)₃]²⁺, including [Ru(CO)₃Cl(glycinate)] (CORM‐3), have been shown to produce ROS through a water–gas shift reaction, which contributes significantly, for example, to their antibacterial activity. In contrast, NAC‐CORM conjugates do not produce ROS or possess antibacterial activity. In addition, we demonstrate the synergistic effect of CO and NAC both for the inhibition of nitric oxide (formation) and in the expression of tumour‐necrosis factor (TNF)‐α. This work highlights the advantages of combining a CO‐releasing scaffold with the anti‐oxidant and anti‐inflammatory drug NAC in a unique pro‐drug.     

An improved HPLC method for the investigation of L‐selenomethionine metabolism in rat gut contents

Selenomethionine (SeMet) is a widely used nutritional supplement that has potential benefit for people living in selenium‐deficient areas. Previous research has shown that selenium administered as SeMet undergoes significant enterohepatic recycling which may involve the gut microflora. In order to investigate this we have developed a simple method for the quantitation of l ‐SeMet in rat gut content suspensions prepared from jejunum, ileum, caecum and colon. After incubation of l ‐SeMet with gut content suspensions, samples were deproteinized with sulfosalicylic acid and derivatized with o‐phthaldialdehyde (OPA) and N‐acetyl‐l ‐cysteine (NAC). Mass spectrometry confirmed the formation of a 1:1:1 derivative of l ‐SeMet with OPA and NAC. Samples were analysed by reversed‐phase high‐performance liquid chromatography with fluorescence detection. The assay was linear in the concentration range 0.5–100 µg/mL (r² = 0.9992) with a limit of detection of 0.025 µg/mL (signal‐to‐noise ratio of 5). Intra‐day and inter‐day accuracies were 91.1–92.8 and 91.7–95.5%, respectively with corresponding precisions as relative standard deviation of <5%. Incubation of l ‐SeMet with gut content suspensions from different parts of the rat intestine showed that l ‐SeMet metabolism occurs mainly in the caecum. Copyright © 2009 John Wiley & Sons, Ltd.     

HPLC determination of acidic d‐amino acids and their N‐methyl derivatives in biological tissues

d ‐Aspartate (d ‐Asp) and N‐methyl‐d ‐aspartate (NMDA) occur in the neuroendocrine systems of vertebrates and invertebrates, where they play a role in hormone release and synthesis, neurotransmission, and memory and learning. N‐methyl‐d ‐glutamate (NMDG) has also been detected in marine bivalves. Several methods have been used to detect these amino acids, but they require pretreatment of tissue samples with o‐phthaldialdehyde (OPA) to remove primary amino acids that interfere with the detection of NMDA and NMDG. We report here a one‐step derivatization procedure with the chiral reagent N‐α‐(5‐fluoro‐2,4‐dinitrophenyl)‐(d or l )‐valine amide, FDNP‐Val‐NH₂, a close analog of Marfey's reagent but with better resolution and higher molar absorptivity. The diastereomers formed were separated by HPLC on an ODS‐Hypersil column eluted with TFA/water–TFA/MeCN. UV absorption at 340 nm permitted detection levels as low as 5–10 pmol. d ‐Asp, NMDA and NMDG peaks were not obscured by other primary or secondary amino acids; hence pretreatment of tissues with OPA was not required. This method is highly reliable and fast (less than 40 min HPLC run). Using this method, we detected d ‐Asp, NMDA and NMDG in several biological tissues (octopus brain, optical lobe and bucchal mass; foot and mantle of the mollusk Scapharca broughtonii), confirming the results of other researchers. Copyright © 2009 John Wiley & Sons, Ltd.     

Ultrasensitive and Simple Method for Determination of N‐Acetyl‐L‐Cysteine in Drug Formulations Using a Diamond Sensor

A boron‐doped diamond (BDD) electrode coupled to flow injection analysis (FIA) was firstly developed for determination of N‐acetyl‐L ‐cysteine (NAC) in drug formulations. The effects of experimental parameters including pH, applied potential and scan rate on the response were investigated. FIA amperometry was applied as an automatic method for the quantitative detection of trace amounts of NAC. A wide linear range of 0.5–50 µmol/L and a low detection limit of 10 nmol/L were obtained. The results of amperometric determinations show a very good reproducibility, and the RSD for the measurement based on 10 measurements was <3.7 % and <4.1 % for intra‐ and inter‐day, respectively. The benefits of the proposed method are fast, simple, sensitive and no requirement of complicated operational steps.     

Preparation of carboxymethyl cellulose‐g‐poly (acrylamide)/montmorillonite superabsorbent composite as a slow‐release urea fertilizer

A superabsorbent composite was synthesized through free‐radical graft copolymerization of carboxymethyl cellulose, acrylamide, and montmorillonite by means of a crosslinker such as N,N′‐methylenebisacrylamide and potassium persulfate as an initiator. The preparation mechanism was proposed, and the composite structures were confirmed by using Fourier transform infrared spectroscopy, X‐ray diffraction, thermal gravimetric analysis, and scanning electron microscope. The factors influencing the swelling capacity of the composite were determined to accomplish the highly swelling capacity. The composition (15 wt% carboxymethyl cellulose, 5.4 wt% montmorillonite, 82 wt% acrylamide, 0.07 wt% N,N′‐methylenebisacrylamide, and 1.1 wt% potassium persulfate) exhibited high swelling capacity; it was selected to be loaded with urea fertilizer, and the release was investigated by measuring the conductivity. The results showed that the new controlled release system has good slow release properties.     

Pharmacokinetics of TAK‐875 and its toxic metabolite TAK‐875‐ acylglucuronide in rat plasma by liquid chromatography tandem mass spectrometry

TAK‐875 is a selective partial agonist of human GPR40 receptor, which was unexpectedly terminated at phase III clinical trials owing to its severe hepatotoxicity. The purpose of this study was to investigate the pharmacokinetics of TAK‐875 and its toxic metabolite TAK‐875‐acylglucuronide in rat plasma by liquid chromatography tandem mass spectrometry (LC–MS/MS). Plasma samples were extracted with ethyl acetate and chromatographic separations were achieved on a C₁₈ column with water and acetonitrile containing 0.05% ammonium hydroxide as mobile phase. The sample was detected in selected reaction monitoring mode with precursor‐to‐product ion transitions being m/z 523.2 → 148.1, m/z 699.3 → 113.1 and m/z 425.2 → 113.1 for TAK‐875, TAK‐875‐acylglucuronide and IS, respectively. The assay showed good linearity over the tested concentration ranges (r > 0.9993), with the LLOQ being 0.5 ng/mL for both analytes. The extraction recovery was >78.45% and no obvious matrix effect was detected. The highly sensitive LC–MS/MS method has been further applied for the pharmacokinetic study of TAK‐875 and its toxic metabolite TAK‐875‐acylglucuronide in rat plasma. Pharmacokinetics results revealed that oral bioavailability of TAK‐875 was 86.85%. The in vivo exposures of TAK‐875‐acylglucuronide in terms of AUC_0–t were 17.54 and 22.29% of that of TAK‐875 after intravenous and oral administration, respectively.     

Stability studies of potent opioid analgesic,morphine‐6‐O‐sulfate in various buffers and biological matrices by HPLC‐DAD analysis

The 6‐O‐ sulfate ester of morphine (M6S) has previously been shown to be an analgesic with greater potency and fewer side effects than morphine. However, being a sulfate ester derivative of morphine, the question exists as to whether this compound is stable in biological fluids and tissues with regard to pH‐ and esterase‐mediated degradation. To date, no studies have focused on the stability profile of M6S across the physiologically relevant pH range of 1.2–7.4. In addition, the stability of M6S is not known in rat plasma and rat brain homogenate, or in simulated rat gastric and intestinal fluids. This study determines the stability profile of M6S (utilized as the sodium salt) and demonstrates that M6S is highly stable and resilient to either enzymatic‐ or pH‐dependent hydrolysis in vitro .     

A highly sensitive LC‐MS/MS method for the determination of S‐citalopram in rat plasma: application to a pharmacokinetic study in rats

A highly sensitive, rapid assay method has been developed and validated for the estimation of S‐citalopram (S‐CPM) in rat plasma with liquid chromatography coupled to tandem mass spectrometry with electrospray ionization in the positive‐ion mode. The assay procedure involves a simple liquid–liquid extraction of S‐CPM and phenacetin (internal standard, IS) from rat plasma with t‐butyl methyl ether. Chromatographic separation was operated with 0.2% formic acid:acetonitrile (20:80, v/v) at a flow rate of 0.50 mL/min on a Symmetry Shield RP₁₈ column with a total run time of 3.0 min. The MS/MS ion transitions monitored were 325.26 → 109.10 for S‐CPM and 180.10 → 110.10 for IS. Method validation and pre‐clinical sample analysis were performed as per FDA guidelines and the results met the acceptance criteria. The lower limit of quantitation achieved was 0.5 ng/mL and the linearity was observed from 0.5 to 5000 ng/mL. The intra‐ and inter‐day precisions were in the range of 1.14–5.56 and 0.25–12.3%, respectively. This novel method has been applied to a pharmacokinetic study and to estimate brain‐to‐plasma ratio of S‐CPM in rats. Copyright © 2010 John Wiley & Sons, Ltd.     

Alleviating Cellular Oxidative Stress through Treatment with Superoxide‐Triggered Persulfide Prodrugs

Overproduction of superoxide anion (O₂^.?), the primary cellular reactive oxygen species (ROS), is implicated in various human diseases. To reduce cellular oxidative stress caused by overproduction of superoxide, we developed a compound that reacts with O₂^.? to release a persulfide (RSSH), a type of reactive sulfur species related to the gasotransmitter hydrogen sulfide (H₂S). Termed SOPD‐NAC , this persulfide donor reacts specifically with O₂^.?, decomposing to generate N‐acetyl cysteine (NAC) persulfide. To enhance persulfide delivery to cells, we conjugated the SOPD motif to a short, self‐assembling peptide (Bz‐CFFE‐NH₂) to make a superoxide‐responsive, persulfide‐donating peptide ( SOPD‐Pep ). Both SOPD‐NAC and SOPD‐Pep delivered persulfides/H₂S to H9C2 cardiomyocytes and lowered ROS levels as confirmed by quantitative in vitro fluorescence imaging studies. Additional in vitro studies on RAW 264.7 macrophages showed that SOPD‐Pep mitigated toxicity induced by phorbol 12‐myristate 13‐acetate (PMA) more effectively than SOPD‐NAC and several control compounds, including common H₂S donors.     

Simultaneous determination of N‐ethylpentylone,dopamine, 5‐hydroxytryptamine and their metabolites in rat brain microdialysis by liquid chromatography tandem mass spectrometry

N‐Ethylpentylone (NEP) is a popular synthetic cathinone abused worldwide. To obtain more information about its pharmacokinetics and pharmacodynamics, a rapid, simple and sensitive liquid chromatography–tandem mass spectrometry method was developed for the determination of NEP, two important neurotransmitters, dopamine and serotonin, and their metabolites, including 3,4‐dihydroxyphenylacetic acid, 3‐methoxytyramine and 5‐hydroxyindole‐3‐acetic acid, in rat brain microdialysate. The analytes were separated on a Phnomenex Polar C₁₈ column, with a mobile phase of 0.1% formic acid in water (A) and 0.1% formic acid in acetonitrile (B) under gradient elution to shorten the total chromatographic run time. A triple quadruple mass spectrometer coupled with an electrospray ionization source in both positive and negative ion mode was used to detect the analytes. This method showed excellent accuracy (87.4–113.5%) and precision (relative standard deviation <15%) at three quality control levels. The limits of detection were 0.2 ng/mL for NEP and 0.2–50 nm for the others and good linearity was obtained. This study pioneered a method to integrate exogenous drugs and endogenous neurotransmitters as the drugs act on the same determination system, which means that this innovation can provide support for further study of the addictive effects of NEP or other synthetic cathinones on extracellular levels of dopamine and 5‐hydroxytryptamine.     

Bis‐tert‐Alcohol‐Functionalized Crown‐6‐Calix[4]arene: An Organic Promoter for Nucleophilic Fluorination

A bis‐tert‐alcohol‐functionalized crown‐6‐calix[4]arene (BACCA) was designed and prepared as a multifunctional organic promoter for nucleophilic fluorinations with CsF. By formation of a CsF/BACCA complex, BACCA could release a significantly active and selective fluoride source for S_N2 fluorination reactions. The origin of the promoting effects of BACCA was studied by quantum chemical methods. The role of BACCA was revealed to be separation of the metal fluoride to a large distance (>8 Å), thereby producing an essentially “free” F^?. The synergistic actions of the crown‐6‐calix[4]arene subunit (whose O atoms coordinate the counter‐cation Cs⁺) and the terminal tert‐alcohol OH groups (forming controlled hydrogen bonds with F^?) of BACCA led to tremendous efficiency in S_N2 fluorination of base‐sensitive substrates.     

Relationship among drug delivery behavior,degradation behavior and morphology of copolylactones derived from glycolide,l‐lactide and ε‐caprolactone

A series of copolylactones was synthesized by ring‐opening copolymerization of glycolide, L ‐lactide and ?‐caprolactone, using stannous octoate as catalyst. The in vitro degradation behaviors of them were studied and data demonstrated different degradation rates which mainly depended on the compositions. Investigation of the 5‐fluorouracil (5‐Fu) release from these copolylactones revealed that the composition, degradation rate and the morphology of the polymeric matrix played an important role on the drug release kinetics. A sustained 5‐Fu release without initial time lag was obtained from random poly(lactide‐co‐glycolide‐co‐caprolactone) (r‐PGLC) drug carrier, and it differed from the cases of polylactide (PLA) or random poly(lactide‐co‐glycolide) (PLGA), which usually showed an initial time lag or biphasic drug release behavior. It was due to the low glass transition temperature (T _g) of the r‐PGLC and the drug would diffuse faster in rubbery state under the experimental temperature. Furthermore, a significant change in the drug release behavior of r‐PGLC was observed when the temperatures were changed around the T _g of the drug carrier, which implied that the drug release behavior could be regulated by adjusting the morphology of the drug carrier. Copyright © 2002 John Wiley & Sons, Ltd.     

A p‐Hydroxyphenacyl–Benzothiazole–Chlorambucil Conjugate as a Real‐Time‐Monitoring Drug‐Delivery System Assisted by Excited‐State Intramolecular Proton Transfer

Among the well‐known phototriggers, the p‐hydroxyphenacyl (pHP) group has consistently enabled the very fast, efficient, and high‐conversion release of active molecules. Despite this unique behavior, the pHP group has been ignored as a delivery agent, particularly in the area of theranostics, because of two major limitations: Its excitation wavelength is below 400 nm, and it is nonfluorescent. We have overcome these limitations by incorporating a 2‐(2′‐hydroxyphenyl)benzothiazole (HBT) appendage capable of rapid excited‐state intramolecular proton transfer (ESIPT). The ESIPT effect also provided two unique advantages: It assisted the deprotonation of the pHP group for faster release, and it was accompanied by a distinct fluorescence color change upon photorelease. In vitro studies showed that the p‐hydroxyphenacyl–benzothiazole–chlorambucil conjugate presents excellent properties, such as real‐time monitoring, photoregulated drug delivery, and biocompatibility.     

Synthesis and biological evaluation of a novel 99mTc‐cyclopentadienyltricarbonyl technetium complex as a new potential brain perfusion imaging agent

A new cytectrene prototype of general formula RCpTc(CO)₃ (R = C₆H₅NHCO, Cp = cyclopentadienyl moiety) has been synthesized from N‐phenylferrocenecarboxamide 2 , characterized and evaluated as a potential brain perfusion imaging agent. An improved procedure has been developed to obtain both the ligand 2 , characterized by its solid‐state structure (orthorhombic, Pccn, a = 10.4443(2) Å, b = 26.1467(6) Å, c = 9.9977(3) Å), and the corresponding metallic Tc‐ and Re‐complexes in good yield. These latter complexes possessed similar HPLC retention times, thereby indicating identity of their molecular structures. The Tc‐complex ^99m Tc‐2 is lipophilic enough to cross the blood‐brain barrier. This complex exhibits good brain uptake (1.41% injected dose per gram tissue at 5 min) combined with a fairly good retention of radioactivity in brain (0.48% injected dose per gram tissue after 1 h). Then, the distribution of the activity at 5 min post‐injection in various rat brain regions showed a higher accumulation in the hippocampus area. The new ^99mTc‐cyclopentadienyltricarbonyl technetium complex reported here showed promising biological results, making it an interesting base for the development of a new generation of cytectrene as brain perfusion imaging agent. Copyright © 2011 John Wiley & Sons, Ltd.     

Fabrication of Nanocomposite Containing Naphthoquinone and Nanogold Supported on Poly(2,6‐pyridinedicarboxylic acid) Film for Voltammetric Determination of N‐Acetyl‐L‐Cysteine

A modified electrode was fabricated by grafting of poly (2,6‐pyridinedicarboxylic acid) film (PDC) by electropolymerization of 2,6‐pyridinedicarboxylic acid on the glassy carbon electrode (GCE). Then, gold nanoparticles (NG) and 1,2‐naphthoquinone‐4‐sulfonic acid sodium (Nq) were immobilized on the PDC/GCE to prepare Nq/NG/PDC/GCE by immersing electrode into NG and Nq solution, respectively. The Nq species on NG/PDC/GCE could catalyze electrooxidation of N‐acetyl‐L ‐cysteine (NAC) with lowering the over potential by about 600 mV. This method used for detection of NAC in dynamic range from 4.0×10^?6 M to 1.30×10^?4 M with a detection of limit (2σ) 8.0×10^?7 M.