Liquid chromatography tandem mass spectrometry method for determination of <i>N</i>‐acetylcysteine in human plasma using an isotope‐labeled internal standard

Lü, Chuan; Liu, Gangyi; Jia, Jingying; Gui, Yan; Liu, Yanmei; Zhang, Mengqi; Liu, Yun; Li, Shuijun; Chen, Yu

doi:10.1002/bmc.1465

Cited by 16 publications

(15 citation statements)

References 33 publications

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“…Interestingly, a large effect on imipenem activity can be observed at concentrations of NAC as low as 0.8 mg/ml (equivalent to 5 mM), which are in the range of concentrations attainable in plasma after intravenous administration (23) or in lungs after its administration via nebulization (21). However, the mean plasma concentration of NAC after oral administration is far below the concentration of NAC necessary to affect imipenem activity (24), even in patients with end-stage renal disease (25). When the NAC/IMI antagonism was studied in the oprD mutant derivative, the PAOD1 variant, the FICi value was 9 (Fig.…”

Section: Fig 2 Antagonistic Effect Of Nac On Imipenem Activity Diffementioning

confidence: 99%

N-Acetylcysteine Selectively Antagonizes the Activity of Imipenem in Pseudomonas aeruginosa by an OprD-Mediated Mechanism

Rodríguez-Beltrán

Cabot²,

Valencia

et al. 2015

Antimicrob Agents Chemother

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The modulating effect of N-acetylcysteine (NAC) on the activity of different antibiotics has been studied in Pseudomonas aeruginosa. Our results demonstrate that, in contrast to previous reports, only the activity of imipenem is clearly affected by NAC. MIC and checkerboard determinations indicate that the NAC-based modulation of imipenem activity is dependent mainly on OprD. SDS-PAGE of outer membrane proteins (OMPs) after NAC treatments demonstrates that NAC does not modify the expression of OprD, suggesting that NAC competitively inhibits the uptake of imipenem through OprD. Similar effects on imipenem activity were obtained with P. aeruginosa clinical isolates. Our results indicate that imipenem-susceptible P. aeruginosa strains become resistant upon simultaneous treatment with NAC and imipenem. Moreover, the generality of the observed effects of NAC on antibiotic activity was assessed with two additional bacterial species, Escherichia coli and Acinetobacter baumannii. Caution should be taken during treatments, as the activity of imipenem may be modified by physiologically attainable concentrations of NAC, particularly during intravenous and nebulized regimes.A lthough its benefit has been questioned (1), N-acetylcysteine (NAC) is being used for the treatment of numerous disorders, including paracetamol intoxication, doxorubicin cardiotoxicity, ischemia-reperfusion cardiac injury, acute respiratory distress syndrome, bronchitis, chemotherapy-induced toxicity, HIV/ AIDS, heavy metal toxicity, and psychiatric disorders (2). This compound is also sold as a dietary supplement, with claims of antioxidant and liver-protecting effects. The antioxidant activity of NAC has been attributed to its reactivity with ·OH, ·NO2, CO 3 · Ϫ , and thiyl radicals, to its capacity for repair of oxidized key cellular molecules, and to its activity as a precursor for glutathione biosynthesis (2). Because of this mucolytic capacity, it has also been used to facilitate the processing of sputum specimens in bacteriology laboratories (3). The ability of NAC to reduce biofilms, alone or in combination with antimicrobials, has been addressed in several bacterial species (4-6). Furthermore, NAC has been proposed as a treatment in Helicobacter pylori infections (7). NAC utility in reducing sputum viscosity in patients with cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD) (8), likely due to its ability to break disulfide bonds, has also been claimed, although its mechanism of action is not well understood.As a result of an imbalance between the production of reactive oxygen species (ROS) caused by inflammation and their inactivation by the impaired antioxidant systems, CF patients with chronic Pseudomonas aeruginosa lung infection have increased oxidative stress. Therefore, antioxidant interventions, including the use of NAC, have been proposed to reduce the extent of oxidative lesions and the rate of lung deterioration (for a review, see reference 9). However, although controversial results on the improvement of lung f...

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Section: Fig 2 Antagonistic Effect Of Nac On Imipenem Activity Diffementioning

confidence: 99%

N-Acetylcysteine Selectively Antagonizes the Activity of Imipenem in Pseudomonas aeruginosa by an OprD-Mediated Mechanism

Rodríguez-Beltrán

Cabot²,

Valencia

et al. 2015

Antimicrob Agents Chemother

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“…In biological fluids, HPLC has been the most predominant technique for the quantification of ACT and fluorescence detection was applied by using different reagents such as N-(1-pyrenyl) maleimide [29] or ammonium 7-fluorobenzo-2-oxa-1,3-diazole-4-sulphonate (SBD-F) [30] as precolumn fluorescence labeling reagents while ortho-phthalaldehyde was used for post column derivatization [31]. Moreover, liquid chromatography tandem mass spectrometry (LC-MS/MS) was a powerful tool applied for the estimation of ACT in plasma and urine [32,33].…”

Section: Research Articlementioning

confidence: 99%

Spectrofluorimetric Estimation of Some Sulfhydryl–Containing Drugs by Demasking Reaction of the Palladium Chelate of 8-Hydroxyquinoline-5-Sulfonic Acid

Rs¹,

Sf²,

Hewala³

et al. 2017

Pharm Anal Acta

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A simple and sensitive spectrofluorimetric method has been developed for the determination of some selected sulfhydryl-containing drugs namely Acetylcysteine (ACS), Captopril (CAP) and Mesna (MSN).The method is based on the interaction of the drugs with potassium (5-sulfoxino) palladium II in alkaline medium in presence of magnesium ions, where the sulfhydryl group combines with palladium from the non-fluorescent potassium bis (5-sulfoxino) palladium II. The resulting 8-hydroxy-5-quinoline sulfonic acid coordinates with magnesium to form the fluorescent chelate that is a measure of the amount of sulfhydrl containing drug analyzed. The fluorescence intensity was measured at an emission wavelength of 485 nm, by excitation at 345 nm. All the experimental parameters affecting the reaction were studied and optimized. The proposed method was applicable over the concentration range of 0.04-0.44 µg/mL for the three drugs and was applied for their determination in bulk form and in pharmaceutical preparations without interference from common excipients. The assay results were statistically compared with those obtained from previously reported methods where no significant difference was found between them. The selectivity and the stability-indicating aspect of the proposed method were confirmed by preparing the disulphides of the studied drugs and applying the reaction to the parent drugs in presence of their disulphides where no interference was detected from these related substances. By virtue of its high sensitivity, the proposed method was also extended to analyze the drugs in spiked human plasma and urine.

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“…20 Due to its anti-oxidative properties, NAC has also played important roles as a potential therapeutic agent in the treatment of diseases caused by free radical production and oxidative damage. 21,22 Several methods have been proposed for the determination of NAC, including chromatography, 23,24 mass spectrometry, 25 spectrophotometry, 26 electrochemistry, 27 chemiluminescence, 28 and electrophoresis. 29 However, these methods exhibited some disadvantages such as complex operation, low detection efficiency and poor anti-interference ability.…”

Section: Introductionmentioning

confidence: 99%

Poly(thymine)-templated fluorescent copper nanoparticles for label-free detection of N-acetylcysteine in pharmaceutical samples

et al. 2015

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26In this paper, a novel and label-free fluorescent sensing strategy has been 27 developed for thiol-containing drugs detection by using poly(thymine) (poly 28 T)-templated copper nanoparticles (Cu NPs) as fluorescent probes. N-acetylcysteine 29 (NAC), one of thiol-containing drugs, was selected as a model case in this strategy. 30 The fluorescence intensity of poly T-templated Cu NPs was found to be quenched 31 effectively with the increasing concentration of NAC, due to the formation of a 32 coordination complex by the Cu-S metal-ligand bond between the NAC and poly 33 T-tempaled Cu NPs. However, the fluorescence intensity was not nearly changed in 34 the presence of other analytes at a 10-fold higher concentration. Under the optimized 35 conditions, the label-free fluorescent sensor achieved highly sensitive and selective 36 detection of NAC with a linear range from 0.2 µM to 100 µM and a detection limit of 37 50 nM. Furthermore, the method was successfully applied in the detection of NAC in 38 pharmaceutical samples. The strategy was free of any fluorescence dye label or 39 complex DNA sequence design, and all the process were performed within 20 minutes 40 at room temperature. Therefore, it could offer a simple, cost-effective, selective and 41 label-free sensing platform for fluorescent detection of thiol-containing drugs in 42 clinical diagnostics. 43 44

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Liquid chromatography tandem mass spectrometry method for determination of N‐acetylcysteine in human plasma using an isotope‐labeled internal standard

Cited by 16 publications

References 33 publications

N-Acetylcysteine Selectively Antagonizes the Activity of Imipenem in Pseudomonas aeruginosa by an OprD-Mediated Mechanism

N-Acetylcysteine Selectively Antagonizes the Activity of Imipenem in Pseudomonas aeruginosa by an OprD-Mediated Mechanism

Spectrofluorimetric Estimation of Some Sulfhydryl–Containing Drugs by Demasking Reaction of the Palladium Chelate of 8-Hydroxyquinoline-5-Sulfonic Acid

Poly(thymine)-templated fluorescent copper nanoparticles for label-free detection of N-acetylcysteine in pharmaceutical samples

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