**4. EIS in drug analysis**

The effects of presence of the PhAMs either in waste and drinking water or even in wastewater treatment plants (WWTPs) are still inarticulate. However, what is well understood is that the impact extends to humans and animal's health, the aquatic environment, and in the long run the ecosystem. This effect is greatly dependent on the released dose of the PhAMs as well as their pharmacological effects. The issue becomes of concern when we know that the metabolites might be of a higher risk than the parent drug compound. At the microbial level, microorganisms upon prolonged exposure to anti-infectives, for example, become more tolerant, and new strains, which cannot be cured using the conventional antimicrobials, are now in the scene [55–57].

EIS, being capable of detecting as low as 10<sup>−</sup>12 M of the target analyte, is widely used in drug analysis. Several drug categories were analyzed using EIS. **Table 1** shows some examples of drugs analyzed using EIS, as well as the matrices and type of electrode used together with the sensing interface, sensing strategy (label-free or labelled), and limit of detection (LoD).

The electrochemical properties of raloxifene, an important chemotherapeutic agent, were assessed using different techniques including EIS. Three electrodes were tested for this investigation: (1) bare screen-printed carbon electrode (SPCE), (2) graphene oxide (GO)/glassy carbon electrode (GCE), and (3) neodymium sesquioxide nanoparticles Nd2O5 NPs@GO/GCE. The target was to assess the interface properties of these electrodes. Results showed that the Rct of the third electrode was much smaller than the other electrodes. Other electrochemical techniques such as cyclic voltammetry (CV) were used in the same work [58].

Other examples included the determination of an important class of PhAMs, which is antibiotics, a subclass of antimicrobials. Label-free detection of oxytetracycline (OTC) in milk samples was performed using a mixture of iron oxide and mesoporous carbon (Fe3O4@mC) together with nanocomposites made of Fe(II) based metal-organic frameworks (525-MOF) by calcination at different temperatures. The sensor showed a very high sensitivity with a LoD = 0.027 pg mL<sup>−</sup><sup>1</sup> and a linear range of 0.005–1.0 ng mL<sup>−</sup><sup>1</sup> . Moreover, the fabricated aptasensor showed a high selectivity for oxytetracycline in the presence of similar drugs like tetracycline, doxycycline, and chlortetracycline [59].

Similarly, label-free detection of tetracycline (TET) was performed using two aptasensors made of carbon paste electrode (CPE) with oleic acid (OA) and a magnetic bar carbon paste electrode (MBCPE) with Fe3O4 magnetic nanoparticles and oleic acid (OA) following the modification of electrode surfaces using anti-TET. The LoD were 1.0 × 10<sup>−</sup>12 to 1.0 × 10−<sup>7</sup> M and 3.0 × 10<sup>−</sup>13 M for the two aptasensors, respectively, and the sensors were applied to pharmaceutical formulations, serum samples, as well as food products (milk and honey) [60].

A sensor based on nanocomposites of mC with SnOx and TiO2 nanocrystals was used to determine tobramycin (TOB) in urine and serum samples selectively and in the presence of kanamycin, oxytetracycline, and doxycycline. The aptasensor showed an excellent sensitivity with a LoD of 0.01 nM [61].

Chloramphenicol was also determined in eye drop formulations using N-doped graphene nano-sheet-Au NP composite (Au/N-G). The LoD was 0.59 μM, and the sensor showed a selectivity in the presence of interferences like oxytetracycline, chlortetracycline, ascorbic acid, and metronidazole [62]. Other applications included sulphamethoxazole using molecularly imprinted polymers (MIPs) decorated with Fe3O4 magnetic nanoparticles (MNPs) on SPCE [63].

Immunosensors for 17β-estradiol composed of Au electrode nanoparticlethiolated protein G-scaffold. This structure has facilitated the anchoring of a mouse monoclonal anti-estradiol antibody. The LoD was 26 pg mL<sup>−</sup><sup>1</sup> . As per the authors, square wave voltammetry (SWV) was more sensitive (18 pg mL<sup>−</sup><sup>1</sup> ) and required less time and effort compared to EIS [64].

**145**

**Target drug**

Raloxifene

OTC TET

Aptasensor (Fe

O3 Aptasensor 1:

CPE

Tablets, milk, honey, and

serum

MBCPE

CPE/OA/anti-TET

Aptasensor 2: MBCPE/Fe

anti-TET

Aptasensor/ SnO

 @TiO x

Au/N-G

GCE

Eye drops

@mC 2

GCE

Urine and serum

EIS

0.01 nM

(Label-free)

EIS

0.59 μM

[62]

(Label-free)

EIS

0.001 nM

[63]

(Label-free)

EIS

26 pg mL*−*1

[64]

(Label-free)

EIS

0.045 pM

[65]

(Labelled detection)

EIS

0.90 ng

[66]

mL*−*1

(Labelled detection)

TOB Chloramphenicol

Sulphamethoxazole

17β-estradiol

BPA

P4 **Table 1.** *Applications of EIS in analysis and characterizations of different drug materials in variable matrices.*

Au nanoparticle-thiolated protein

Au

Serum

G-scaffold

AuNPs/PB/CNTs-COOH/GCE

ssDNA/Au

Au

Tap water

GCE

Water

MIP-decorated Fe

O3

4 MNPs

SPCE

Seawater

O3

4

NPs/OA/

@mC 4

900)

GCE

Milk samples

Nd

O2

5 NPs@GO/GCE

GCE

ND

Serum and urine

**Sensing interface**

**Electrode**

**Matrix**

**Sensing measurement method and strategy**

EIS

ND

[58]

ND

18.43 nM

CV

Amperometry

(Label-free)

EIS

0.027 pg

[59]

mL−1

10−1

*–*10−7 M

[60]

3.0 × 10−13 M

(Label-free)

EIS

(Label-free)

**LoD**

**Ref**

*Electrochemical Impedance Spectroscopy (EIS) in Food, Water, and Drug Analyses: Recent…*

[61]

*DOI: http://dx.doi.org/10.5772/intechopen.92333*


*Electrochemical Impedance Spectroscopy (EIS) in Food, Water, and Drug Analyses: Recent… DOI: http://dx.doi.org/10.5772/intechopen.92333*

> **Table 1.**

 *Applications of EIS in analysis and characterizations of different drug materials in variable matrices.*

*Electrochemical Impedance Spectroscopy*

bials, are now in the scene [55–57].

labelled), and limit of detection (LoD).

linear range of 0.005–1.0 ng mL<sup>−</sup><sup>1</sup>

LoD were 1.0 × 10<sup>−</sup>12 to 1.0 × 10−<sup>7</sup>

doxycycline, and chlortetracycline [59].

samples, as well as food products (milk and honey) [60].

showed an excellent sensitivity with a LoD of 0.01 nM [61].

rated with Fe3O4 magnetic nanoparticles (MNPs) on SPCE [63].

monoclonal anti-estradiol antibody. The LoD was 26 pg mL<sup>−</sup><sup>1</sup>

less time and effort compared to EIS [64].

square wave voltammetry (SWV) was more sensitive (18 pg mL<sup>−</sup><sup>1</sup>

work [58].

what is well understood is that the impact extends to humans and animal's health, the aquatic environment, and in the long run the ecosystem. This effect is greatly dependent on the released dose of the PhAMs as well as their pharmacological effects. The issue becomes of concern when we know that the metabolites might be of a higher risk than the parent drug compound. At the microbial level, microorganisms upon prolonged exposure to anti-infectives, for example, become more tolerant, and new strains, which cannot be cured using the conventional antimicro-

EIS, being capable of detecting as low as 10<sup>−</sup>12 M of the target analyte, is widely

The electrochemical properties of raloxifene, an important chemotherapeutic agent, were assessed using different techniques including EIS. Three electrodes were tested for this investigation: (1) bare screen-printed carbon electrode (SPCE), (2) graphene oxide (GO)/glassy carbon electrode (GCE), and (3) neodymium sesquioxide nanoparticles Nd2O5 NPs@GO/GCE. The target was to assess the interface properties of these electrodes. Results showed that the Rct of the third electrode was much smaller than the other electrodes. Other electrochemical techniques such as cyclic voltammetry (CV) were used in the same

Other examples included the determination of an important class of PhAMs, which is antibiotics, a subclass of antimicrobials. Label-free detection of oxytetracycline (OTC) in milk samples was performed using a mixture of iron oxide and mesoporous carbon (Fe3O4@mC) together with nanocomposites made of Fe(II) based metal-organic frameworks (525-MOF) by calcination at different temperatures. The sensor showed a very high sensitivity with a LoD = 0.027 pg mL<sup>−</sup><sup>1</sup>

high selectivity for oxytetracycline in the presence of similar drugs like tetracycline,

Similarly, label-free detection of tetracycline (TET) was performed using two aptasensors made of carbon paste electrode (CPE) with oleic acid (OA) and a magnetic bar carbon paste electrode (MBCPE) with Fe3O4 magnetic nanoparticles and oleic acid (OA) following the modification of electrode surfaces using anti-TET. The

respectively, and the sensors were applied to pharmaceutical formulations, serum

A sensor based on nanocomposites of mC with SnOx and TiO2 nanocrystals was used to determine tobramycin (TOB) in urine and serum samples selectively and in the presence of kanamycin, oxytetracycline, and doxycycline. The aptasensor

Chloramphenicol was also determined in eye drop formulations using N-doped graphene nano-sheet-Au NP composite (Au/N-G). The LoD was 0.59 μM, and the sensor showed a selectivity in the presence of interferences like oxytetracycline, chlortetracycline, ascorbic acid, and metronidazole [62]. Other applications included sulphamethoxazole using molecularly imprinted polymers (MIPs) deco-

Immunosensors for 17β-estradiol composed of Au electrode nanoparticlethiolated protein G-scaffold. This structure has facilitated the anchoring of a mouse

. Moreover, the fabricated aptasensor showed a

M and 3.0 × 10<sup>−</sup>13 M for the two aptasensors,

and a

. As per the authors,

) and required

used in drug analysis. Several drug categories were analyzed using EIS. **Table 1** shows some examples of drugs analyzed using EIS, as well as the matrices and type of electrode used together with the sensing interface, sensing strategy (label-free or

**144**

Bisphenol A (BPA), a xenoestrogen with an estrogen-mimicking effect and that is widely used as a precursor in plastics industry, has been determined using a labelled aptasensor made of gold nanoparticles (AuNPs), Prussian blue (PB), and functionalized carbon nanotubes (AuNPs/PB/CNTs-COOH).

Determination of progesterone (P4) in water and other clinical samples was performed using single-stranded ssDNA aptamers with high binding affinity to P4 [66].
