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A facile nano-iron oxide sensor for the electrochemical detection of the anti-diabetic drug linagliptin in the presence of glucose and metformin
Bulletin of the National Research Centre volume 43, Article number: 95 (2019)
A highly sensitive sensor for the electrochemical determination of an antidiabetic drug Linagliptin (LG) was constructed using carbon paste electrode (CPE) modified with iron oxide nanoparticles (Fe2O3NPs). The electrochemical performance of LG was examined analytically, and some dynamics were considered for the first time.
This work indicates that the oxidation reaction of LG on CPE/Fe2O3NPs is a one electron and one proton process, which is controlled by both diffusion and adsorption. The simultaneous determination of LG with glucose and metformin (MET) was also considered by square wave voltammetry in universal buffer pH 7.4. Experimental results specify a linear relation between LG peak current and its concentration in the range of 0.03 to 86 μg/ml, leading to a detection limit of 8.0 ng/ml.
This novel sensor was successfully used to determine LG in commercialized tablets and in spiked urine samples.
Finding new methods for the problems in the medical field is the center of researchers everywhere. Diabetes mellitus is a worldwide public health problem. People who have diabetes can develop serious or life-threatening complications, so taking medication(s) may help to manage diabetes and improve health (Association AD 2014). Insulin deficiency and hyperglycemia cause the concentration of blood glucose to increase or decrease than the normal range of 80–120 mg/dL (4.4–6.6 mM), which leads to death (Waldhäusl et al. 1979). The complications of fighting diabetes, include heart disease, kidney failure, or blindness, which can be reduced through personal control of blood glucose (Group UPDS 1998). Linagliptin is a dipeptidyl peptidase-4 (DPP-4) inhibitor developed by Boehringer Ingelheim for treatment of type II diabetes in patients who cannot control blood sugar levels alone. Linagliptin works by increasing the amount of insulin released and decreasing the amount of sugar made by the body by slowing the breakdown of insulinotropic hormone glucagon-like peptide (GLP)-1 for better glycemic control.
Combination therapy has a pivotal role in type II diabetes mellitus management in patients unable to maintain normal glycemic level using metformin alone. Addition of linagliptin, dipeptidyl peptidase-IV inhibitor, to metformin improves glycemic control. Various analytical techniques are applied for simultaneous determination of binary diabetes drugs mixture such as LG and MET mixture (Haak 2015) including HPLC with UV detector (Vemula et al. 2015), LC-MS/MS (Abbas Moussa et al. 2019), and UV-Vis diffuse reflectance spectroscopy (El-Bagary et al. 2013). No electrochemical reported work applied for the determination of either the LG or our studied mixture, only voltammetric determination for MET (Brocks et al. 2010).
Magnetic nanoparticles (NPs) are in the focus of much interest especially iron oxide nanoparticles due to their enormous and unique physical and chemical properties. The most considered materials with promising properties are those with magnetic properties due to their enormous and unique physical and chemical properties and applications such as drug delivery, biomedical uses, and tumor labeling (Jalilian et al. 2009; Polyak and Friedman 2009). These applications require that the nanoparticles have high magnetization values, a size smaller than 100 nm, and a narrow particle size distribution. The nano-size of iron oxide nanoparticles and its biocompatibility make them perfect for surface engineering and functionalization (Laurent et al. 2011; Prodan et al. 2013). Also, Fe2O3 NPs provide a path to a new generation of chemical and electrochemical sensors for glucose biosensor applications with some materials such as Pt nanoparticles and multi-walled carbon nanotubes (Li et al. 2010; Rong et al. 2007), Ni oxide nanoparticles (Salimi et al. 2007), and silicon dioxide (Baby and Ramaprabhu 2010). The goal of the present work is to carry out a study on the effect of different parameters such as pH, scan rate, and the effect of changing the percentage of Fe2O3Nps added, on the determination of LG raw material, on pharmaceutical formulation, and in human urine samples.
Linagliptin (LG) was supplied from the European Egyptian Pharmaceutical Industries, Egypt, iron nanoparticles. Graphite powder and paraffin oil were purchased from sigma Aldrich. Universal buffer (B–R buffer) 0.04 M of pH 2–11 (CH3COOH + H3BO3 + H3PO4), was used as the supporting electrolyte, then 0.2 M NaOH was used to gain the desired pH value.
All voltammetric measurements were performed by stationary electrode using 797VA Computrace software (1.0) from Metrohm, Switzerland, electrochemical analyzer. A three-electrode cell system incorporating the carbon paste electrode as a working electrode and the impedance measurements were done by the three-electrode electrochemical workstation EC-Lab SP-150 potentiostat. A platinum wire as an auxiliary electrode was used with respect to calomel reference electrode. Energy-dispersive X-ray measurements were performed by EDX spectroscopy unit of Model Quanta 250 FEG (Field Emission Gun) with accelerating voltage 30 KV.
Preparation of CPE/Fe2O3NP sensor
Carbon paste electrode (CPE) was prepared by mixing graphite powder (0.5 g) with drops of nujol oil in a glass mortar. CPE/Fe2O3NP-modified electrode was prepared by mixing ratios of 5, 10, 12, 15, and 20% modified paste containing 95, 90, 88, 85, and 80 mg of graphite powder and 5, 10, 12, 15, and 20 mg of Fe2O3NP modifier mixed, respectively, with suitable amount of paraffin oil. The components were stirred for 10 min in a glass mortar at room temperature to achieve homogenous paste that was used for voltammetric measurements without preconditioning.
Validation in pharmaceutical samples
Five tablets of the commercial pharmaceutical Trajenta (5 mg LG/Tablet) were powdered and dissolved in deionized water. After supersonic treatment for 30 min, it was filtered and the concentration of LG in the working range was achieved, and then, SWV were recorded using the standard addition method.
Analysis of spiked urine samples
Urine was supplied from healthy volunteers; the spiked urine sample was centrifuged for 10 min at 13,000 rpm to get rid of protein residues, and then, the supernatant was taken carefully. An aliquot (1 mL) of the clear solution was added to a mixture of 9 mL B–R buffer to achieve a final concentration of 1.0 mM, at an optimum pH value to perform a calibration curve.
Figure 1 shows SEM images of the bare CPE and CPE/Fe2O3NP-fabricated electrodes. The surface of the CPE is dominated with microstructure with a heterogeneous grain growth, (Fig. 1a). In Fig. 1b, CPE/Fe2O3NP surface (Shehata et al. 2016) showed small iron oxide nanoparticles placed at different sites over the CPE surface with a cloudy aggregates and uniform distribution, displaying a larger surface area.
Electrochemical impedance spectroscopy scans were measured at peak potential (1050 mV) for bare CPE, and CPE modified with 10%, 12%, 15%, and 20% Fe2O3NPs are shown in (Fig. 2) as Nyquist plots. It shows a semicircle at high frequency indicating a charge transfer process connected to a linear line at low frequency indicating a diffusion process (Azab and Fekry 2017a, 2017b). Thus, the mechanism of the reaction depends on both charge transfer and diffusion processes. The diameter of the semicircle increases in the following order: bare CPE > 10% Fe2O3NPs > 12% Fe2O3NPs > 20% Fe2O3NPs > 15% Fe2O3NPs. The Nyquist plot data were simulated with equivalent circuit (inset) with 2% error. Analysis was performed by Thales software provided with the Zahner-Electric workstation (Polyak and Friedman 2009). The model consists of R4ZwC3, R3C2, and R2C1 in series with the solution resistance (R1). C refers to the capacitance; R is the resistance, and Zw is the Warburg component related to diffusion (Bard et al. 1980). Generally, the data shows that upon the addition of 15% Fe2O3NPs the oxidation of LG gives lower impedance value (highest conductivity) and highest diffusion process (W = 41.7 Ω cm2 s−1/2) compared to W = 37.1 Ω cm2 s−1/2 for the bare CPE, due to large surface area (Azab and Fekry 2017a, 2017b; Mohamed et al. 2017) that NPs provide giving a nano-environment with high electron communication features for the electrochemical detection of LG with fast and good capacity which progress the direct electron movement between the active sites of NPs and LG. The same result was obtained in the SWV of 1.0 mM LG (inset), in which it was clear that the highest anodic peak current was achieved when 15% Fe2O3NPs was used.
The cyclic voltammograms of hexacyanoferrate (II) (Fig. 3) showed well-defined redox peaks for the modified CPE/Fe2O3NPs, with mid-point potential at ca. + 0.450 V vs Ag/AgCl (slightly higher than for the bare CPE at ca. + 0.400 V). The shapes of the CVs were almost unaffected by the scan rate, and both cathodic and anodic peak currents depend linearly on the square root of the scan rate over the entire range of scan rates considered, indicating a diffusion-controlled electrochemical process, with no adsorption on the Fe2O3NP. When Fe2O3NP is cobimbined to the graphite paste, larger differences between oxidation and reduction peaks were observed which slightly increased with increasing scan rate. This is common on carbon electrode surfaces (Yogeswaran and Chen 2007).
Effect of pH: The effect of solution pH on the electrochemical response of LG at CPE/Fe2O3NPs was recorded in B–R buffers and was found to be discerning over the pH range of 2–11. The peak potentials decrease gradually in solutions as pH is raised, manifesting that protons have taken part in the electrode reaction processes. The results show that pH 7 and 9 gave the maximum anodic peak current response, because the surface of iron oxide atoms act as Lewis acids and coordinate with water, which dissociates giving amphoteric hydroxyl group. These hydroxyl groups carry negative charges (Lefebure et al. 1998). And since the pKa value of LG is 9.86, therefore, an electrostatic attraction force was induced between the positively charged LG at alkaline pH values and the negatively charged iron oxide nanoparticles surface which give a high current response. So, the rest of the work will be performed at pH 7.4 (physiological pH of the body).
Effect of varying the scan rate: The effect of varying the scan rate over the range of 10–240 mV/s was considered to detect the diffusion and adsorption characters of 1.0 LG at CPE/Fe2O3NP surface in B–R buffer pH 7.4 using cyclic voltammetry (Fig. 4). The positive shift in the peak potential commends that the oxidation process is irreversible. The relation between the peak current versus square root of scan rate was constructed (inset A) giving a straight line with an equation of Ip (μA) = 1.08√υ – 0.153; R = 0.9994, which indicates mass transfer-controlling process of oxidation via diffusion. Also, a plot of log peak current with log scan rate gives a linear relationship with a slope of 0.494 (inset B), suggesting that LG oxidation on CPE/Fe2O3NPs is mainly controlled by diffusion with some adsorption support.
The surface areas were evaluated to be 0.072 cm2 and 0.143, for CPE and CPE/Fe2O3NPs, respectively, which indicates that the addition of iron oxide nanoparticles doubled the surface area of the sensor and therefore increases the electroactive sites that enhanced the current response of LG.
Also, the determination of the sensor dynamics parameters (α and n) is essential to determine the proposed mechanism of LG, Scheme 1. The relationship between Epa and log ν (inset C) is given by the Laviron equation (Shen et al. 2009):
where α is the electron transfer coefficient, ks is the standard rate constant of the surface reaction, and E0 is the formal potential obtained from the relation between Ep and ν by extrapolating to the vertical axis at ν = 0 and it was found to be 1.04 V, αn can be calculated from the slope of Ep vs. log v (inset C). In this system, the slope is 0.0763, αn was calculated to be 0.777. From the Bard and Faulkner equation (Bard et al. 1980) and the CV plot of LG.
The electron transfer coefficient was found to be 0.53, and then, n was calculated to be 1.2 ≈ 1 which indicated that only one electron was involved in the oxidation of LG. The value of ks can be calculated from the intercept of the Laviron equation and was found to be 1.06 × 102 s−1.
The electrooxidation performance of LG was documented as CV, in the range of 800 to 1300 mV (Fig. 5), in B–R buffer pH 7.4, at a scan rate of 100 mV s−1 for the tested electrodes: (bare CPE) and (CPE/Fe2O3NPs). For bare CPE, the anodic peak oxidation of LG appeared at Ep = 1050 mV with a current value of 2.5 μA. The peak current increases upon adding Fe2O3NPs; this designated that the Fe2O3NPs has increased the sensor surface area. Finally, for 15% modified CPE/Fe2O3NPs, the anodic peak current extended to a highest value of 6.9 μA. This may be attributed to an electrostatic attraction among the cationic LG and the anionic Fe2O3NPs forming hydrogen bond that endorses faster electron transfer developing well the diffusion of LG among the surface. The schematic demonstration for this contact is explained in Fig. 5 inset.
Square wave voltammograms of LG with different concentrations from 0.03 to 86.2 μg/ml using CPE/Fe2O3NPs were presented in Fig. 6. The International Conference on Harmonization (ICH) guidelines (I. H. T. (Guideline 1997)) for method validation were followed for validation of the suggested method. The current response increases steadily as a function of LG concentration, giving a calibration curve with a correlation coefficient of 0.9993 (inset A). Also, the detection limit LOD = 3s/m and the quantification limit LOQ = 10s/m were calculated, where s is the standard deviation and m is the slope of the calibration curves which were found to be 0.008 μg/ml and 0.026 μg/ml, respectively. The high sensitivity of film can be attributed to the increase of the surface area with the iron oxide nanoparticles, the diffusion and adsorption mechanisms, high catalytic activity, and biocompatibility of the iron oxide NPs. The evaluated sensitivity of the fabricated CPE/Fe2O3NP sensor is relatively higher than that of previously reported techniques (Table 1).
This is because the oxidation of Fe2O3NPs in aqueous media, in accordance with the dissolved oxygen (O2) surrounding the electrode surface, leads to an increase in the adsorbed oxygen on the Fe2O3NP surfaces, which therefore increases oxidizing capability of the analyte. According to the following mechanisms (Banik et al. 2015; El-Bagary et al. 2013; Padmaja and Veerabhadram 2015; Bailey and Turner 1996:
Also, the reduced LG donates electrons to Fe2O3NP surface. Therefore, resistance is decreased, or conductance is increased.
Influence of the square wave frequency (f)
The square wave frequency determines the intensity of the signal and the sensitivity of the technique. The relation between the anodic current and the square wave frequency shows a linear relation up to 140 s−1(Fig. 6, inset B). For larger values of frequency, the effect is almost negligible (O’Dea et al. 1993). This behavior corresponds to a totally irreversible process controlled by adsorption of the analyte on the electrode surface. Also, the peak potential should vary linearly with the logarithm of the frequency following the relationship:
A value of 0.66 was determined for αn, and as the electron transfer coefficient was found to be 0.53, therefore, n = 1.2, indicating the transference of 1 electron per LG molecule, confirming the data obtained in the scan rate section. Thus, the suggested mechanism for LG is presented in Scheme 1.
Specificity of the method is monitored by measuring the current response of an analyte in the presence of other interferences. Glucose sensors account for approximately 85% of the biosensor industry. Non-enzymatic glucose electrodes give higher oxidation current response, higher stability, lower cost, and greater sensitivity. Electrocatalytic processes are important for glucose oxidation, since it is a kinetically very slow process with negligible faradaic current, showing a non-diffusion-controlled process (Vassilyev et al. 1985). The electrocatalysis occurs via the adsorption of analyte on the electrode surface, which involves the d-electrons to form bonds with the analyte (Pletcher 1984).
In this work, the specificity was checked by analyzing LG with MET and glucose in laboratory-prepared mixtures using bare CPE and CPE/Fe2O3NPs in Fig. 7. No peak was observed for glucose in case of bare CPE, and only a broad peak was observed for MET and LG, while CPE/Fe2O3NP sensor exhibits three good resolution anodic peaks: the first was for glucose which was oxidized to form glucolactone, which hydrolyses in H2O to form gluconic acid giving an anodic peak current at 260 mV, and the second peak at 760 is due to the oxidation of the imino group in guanidino group to a N-hydroxy imino group of metformin (Jerez et al. 2014), while the third one is due to LG oxidation at 960 mV. Also, linagliptin’s recovery was examined with some related substances that potentially present with LG in the dosage formulation under optimum conditions when the concentration of each constituent was 1.0 × 10−3 M and was found to be 99.66, 98.10, 99.93, 99.60, and 98.92 for glucose, metformin, talc, urea, and starch, respectively.
These results indicate that these substances did not interfere with LG, which confirms the specificity of the proposed method, since the tolerance limit was less than 2%.
Application of linagliptin
In pharmaceutical formulation: For the purpose of the practical applicability of the proposed method and the modified sensor, the SWV method was applied for the investigation of LG in five Trajenta (5 mg/tablet) tablets without any sample extraction to obtain 1.0 mM LG solution. The validity of the proposed method was evaluated by the standard addition technique, and the accuracy has been determined giving satisfactory recoveries from 99.98 to 101.9%, and relative standard deviation from 0.04 to 0.63% reveals that the excipient presented in the tablet does not interfere with the active ingredient. The results suggested that CPE/Fe2O3NPs has high reproducibility and would be useful sensor for quantitative analysis of LG in pharmaceutical formulations.
In spiked urine sample: The validation of CPE/Fe2O3NPs for the quantitative assay of LG in urine was examined in B–R buffer pH 7.4. Six different concentrations on the calibration curve are chosen to be repeated for five times to evaluate the accuracy and precision of the proposed method, which shows a recovery values from 99.9–100.1%. Also, the statistical analysis of the results was obtained by applying the proposed and the reported methods, and the mean ± S.D. of LG in urine sample was found to be 100.05 ± 0.25 for the proposed method with t (2.776) value of 0.575 and F (19) value of 3.760 (n = 4), while the mean ± S.D. for the reported method was found to be 99.95 ± 0.13 when the values between parentheses was 85%.
This work describes a new and very simple CPE sensor for the electrochemical determination of linagliptin in pharmaceutical formulations, in urine samples, and in the presence of glucose and the co-administered drug MET using magnetic iron oxide nanoparticles. Some dynamic parameters are considered for the first time. The results showed that the method was sensitive, precise, and selective with no significant effects of the excipients background. A linear relation between LG peak current and its concentration in the range 0.03 to 86 μg/ml leads to a detection limit of 0.008 μg/ml.
Abbas Moussa B, Mahrouse MA, Fawzy MG (2019) A validated LC-MS/MS method for simultaneous determination of linagliptin and metformin in spiked human plasma coupled with solid phase extraction: application to a pharmacokinetic study in healthy volunteers. J Pharm Biomed Anal 30(163):153–161
Association AD (2014) Standards of medical care in diabetes. Diabetes Care 37:S14–S80
Azab SM, Fekry AM (2017a) A novel electrochemical determination for the anti-osteoporosis drug (alendronate sodium) and its application for corrosion monitoring of surgical 316 L SS bone implant. J Alloy Compd 717:25–30
Azab SM, Fekry AM (2017b) Electrochemical design of a new nanosensor based on cobalt nanoparticles, chitosan and MWCNT for the determination of daclatasvir: a hepatitis C antiviral drug. RSC Adv 7:1118–1126
Baby TT, Ramaprabhu S (2010) SiO2 coated Fe3O4 magnetic nanoparticle dispersed multiwalled carbon nanotubes based amperometric glucose biosensor. Talanta 80:2016–2022
Bailey CJ, Turner RC (1996) Metformin. N Eng L J Med 1996(334):574–579
Banik S, Karmakar P, Miah MAH (2015) Development and validation of a UV-spectrophotometric method for determination of vildagliptin and linagliptin in bulk and pharmaceutical dosage forms. Bangladesh Pharm J 18:163–168
Bard AJ, Faulkner LR, Leddy J, Zoski CG (1980) Electrochemical methods: fundamentals and applicationsEditor. Wiley, New York, p 2
Brocks D, Gabr RQ, Padwal RS (2010) Determination of metformin in human plasma and urine by high-performance liquid chromatography using small sample volume and conventional octadecyl silane column. J Pharm Pharm Sci 13:486–494
Compton R G, Banks C E (2007) Understanding Voltammetry, World Scientific
El-Bagary RI, Elkady EF, Ayoub BM (2013) Spectrophotometric methods for the determination of linagliptin in binary mixture with metformin hydrochloride and simultaneous determination of linagliptin and metformin hydrochloride using high performance liquid chromatography. Int J Biomed Sci 9:41
El-Shal MA, Hendawy HAMH, Eldin GMG, El-Shiref ZA (2019) Application of nano graphene modified electrode as an electrochemical sensor for determination of tapentadol in presence of paracetamol. J Iran Chem Soc. https://doi.org/10.1007/s13738-018-01585-z
Group UPDS (1998) Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet 352:837–853
IHT Guideline (1997) Fed Regist:62
Haak T (2015) Combination of linagliptin and metformin for the treatment of patients with type 2 diabetes. Clin Med Insights Endocrinol Diabetes 8:1
Jalilian A, Panahifar A, Mahmoudi M, Akhlaghi M, Simchi A (2009) Preparation and biological evaluation of [ 67 Ga]-labeled-superparamagnetic nanoparticles in normal rats. Radiochim Acta 97:51–56
Jerez LB, García-Pérez U, Zambrano-Robledo P, Hernández-Moreira J (2014) Carbon paste electrode modified with BiVO4 to sense metformin. Int J Electrochem Sci 9:4643–4652
Laurent S, Dutz S, Häfeli UO, Mahmoudi M (2011) Magnetic fluid hyperthermia: focus on superparamagnetic iron oxide nanoparticles. Adv Colloid Interfac 166:8–23
Lefebure S, Dubois E, Cabuil V, Neveu S, Massart R (1998) Monodisperse magnetic nanoparticles: preparation and dispersion in water and oils. J Mater Res 13:2975–2981
Li J, Yuan R, Chai Y, Che X (2010) Fabrication of a novel glucose biosensor based on Pt nanoparticles decorated iron oxide-multiwall carbon nanotubes magnetic composite. J Mol Catal B Enzym 66:8–14
Mohamed MA, Fekry AM, El-Shal MA, Banks CE (2017) Incorporation of tetrazolium blue (TB)/gold nanoparticles (GNPs) into carbon paste electrode: application as an electrochemical sensor for the sensitive and selective determination of sotalol in micellar medium. Electroanalysis 29:2551
O'Dea JJ, Ribes A, Osteryoung JG (1993) Characterization of quasi-reversible surface processes by square-wave voltammetry. J Electroanal Chem y 345:287–301
Padmaja N, Veerabhadram G (2015) Development and validation of analytical method forsimultaneous estimation of empagliflozin and linaglptin in bulk drugs and combined dosage forms using UV-visiblespectroscopy. Pharm Lett 7:306–312
Pletcher D (1984) Electrocatalysis: present and future. J Appl Electrochem 14:403–415
Polyak B, Friedman G (2009) Magnetic targeting for site-specific drug delivery: applications and clinical potential. Expert Opin Drug Del 6:53–70
Prodan AM, Iconaru SL, Chifiriuc CM, Bleotu C, Ciobanu CS, Motelica-Heino M, Sizaret S, Predoi D (2013) Magnetic properties and biological activity evaluation of iron oxide nanoparticles. J Nanomater 2013:7
Rong LQ, Yang C, Qian QY, Xia XH (2007) Study of the nonenzymatic glucose sensor based on highly dispersed Pt nanoparticles supported on carbon nanotubes. Talanta 72:819–824
Salimi A, Sharifi E, Noorbakhsh A, Soltanian S (2007) Immobilization of glucose oxidase on electrodeposited nickel oxide nanoparticles: direct electron transfer and electrocatalytic activity. Biosens Bioelectron 22:3146–3153
Shehata M, Azab S, Fekry A, Ameer M (2016) Nano-TiO2 modified carbon paste sensor for electrochemical nicotine detection using anionic surfactant. Biosens Bioelectron 79:589–592
Shen Y, Tang J, Nie Z, Wang Y, Ren Y, Zuo L (2009) Preparation and application of magnetic Fe3O4 nanoparticles for waste waterpurification. Sep Purif Technol 68:312–319
Vassilyev YB, Khazova O, Nikolaeva N (1985) Kinetics and mechanism of glucose eiectrooxidation on different electrode-catalysis. J Electroanal Chem Interfacial Electrochem 196:105–125
Vemula P, Dodda D, Balekari U, Panga S, Veeresham C (2015) Simultaneous determination of linagliptin and metformin by reverse phase-high performance liquid chromatography method: an application in quantitative analysis of pharmaceutical dosage forms. J Adv Pharm Technol Res 6(1):25–28
Waldhäusl W, Kleinberger G, Korn A, Dudczak R, Bratusch-Marrain P, Nowotny P (1979) Severe hyperglycemia: effects of rehydration on endocrine derangements and blood glucose concentration. Diabetes 28:577–584
Yogeswaran U, Chen SM (2007) Separation and concentration effect of f-MWCNTs on electrocatalytic responses of ascorbic acid, dopamine and uric acid at f-MWCNTs incorporated with poly (neutral red) composite films. Electrochim Acta 52(19):5985–5996
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El-Shal, M.A., Azab, S.M. & Hendawy, H.A.M. A facile nano-iron oxide sensor for the electrochemical detection of the anti-diabetic drug linagliptin in the presence of glucose and metformin. Bull Natl Res Cent 43, 95 (2019) doi:10.1186/s42269-019-0132-8
- Iron oxide nanoparticles
- Carbon paste electrode