J Solid State Electrochem
DOI 10.1007/s10008-015-3105-3
ORIGINAL PAPER
Determination of prazosin in pharmaceutical samples by flow
injection analysis with multiple-pulse amperometric detection
using boron-doped diamond electrode
Tiago de Jesus Guedes 1 & Morgana F. Alecrim 2 & Fernando M. Oliveira 1 &
Amanda B. Lima 1 & Sandro L. Barbosa 2 & Wallans T. P. dos Santos 2
Received: 18 October 2015 / Revised: 7 December 2015 / Accepted: 14 December 2015
# Springer-Verlag Berlin Heidelberg 2015
Abstract This work describes the development of a simple,
fast and low-cost method for determining prazosin (PRA) in
pharmaceutical samples by flow injection analysis with
multiple-pulse amperometric (FIA-MPA) detection using a
boron-doped diamond film electrode. Electrochemical detec-
tion of PRA was optimized in phosphate buffer pH 4.0 by
cyclic voltammetry, in which PRA presented two oxidation
processes around at 0.97 and 1.40 V versus Ag/AgCl
(3.0 mol L−1 KCl). In these conditions, PRA also showed
one reduction process at −0.75 V that is dependent on the
oxidation processes. Thus, the determination of PRA by
FIA-MPA detection consisted on the application of a two-
potential waveform, E 1 (generator potential) = 1.6 V/
400 ms and E2 (collector potential) = −1.0 V/30 ms, with
sample loop of 150 μL and flow rate of 3.0 mL min−1. The
method showed good repeatability (RSD < 3.0 %) and high
analytical frequency (70 injections per h). The working
linear range was obtained from 2 to 200 μmol L−1 with a
limit of detection of 0.5 μmol L−1. The recovery tests in all
samples were approximately 100 %, and the results were
compared with chromatographic methods.
* Wallans T. P. dos Santos
wallanst@yahoo.com.br
1
Departamento de Química, Universidade Federal dos Vales do
Jequitinhonha e Mucuri, Campus JK, 39100-000 Diamantina, MG,
Brazil
2
Departamento de Farmácia, Universidade Federal dos Vales do
Jequitinhonha e Mucuri, Campus JK, 39100-000 Diamantina, MG,
Brazil
Keywords Prazosin . Pharmaceutical analysis . Boron-doped
diamond . Multiple-pulse amperometry . Flow injection
analysis
Introduction
Prazosin (PRA) is the prototype of a family of agents that
contain a core of piperazinyl quinazoline and acts as a potent
and selective antagonist of α1 receptors, promoting decrease
in peripheral vascular resistance and venous return to the
heart, which consequently leads to its therapeutic effect in
the treatment of hypertension [1]. Its structural formula is
shown in Fig. 1.
PRA is a drug with narrow therapeutic index [2], which
makes its determination very important to analyze this ac-
tive ingredient in formulations for the quality control in
pharmaceutical formulations and in biological fluids for
pharmacological studies. The official methods for determi-
nation of PRA in pharmaceutical formulations are de-
scribed in USP and British Pharmacopoeia [3, 4], which
are based on chromatography (HPLC with UV detection).
It can also be found in the literature various methods for
determination of PRA in formulations and biological fluids
using HPLC with UV detection [5, 6] and other different
detectors: fluorescence [7, 8], rayleigh light-scattering [9],
and amperometric using glassy carbon electrode [10]. In
addition, other methods for determination of PRA, such
as spectrophotometry [11], thin layer chromatography
[12], capillary electrophoresis [13], and electroanalytical
techniques [14–17].
Among all these methods, the electroanalytical techniques
have shown to be an attractive alternativeness for the

Fig. 1 Structural formula of PRA
determination of drugs in pharmaceutical formulations and in
biologic fluids. This is because the electrochemical detec-
tion often presents high selectivity and sensitivity for the
determination of electroactive compounds. Furthermore,
the electroanalytical methods provide low-cost and fast
analysis with less waste generation [18]. However, in the
literature, only four methods were published for PRA de-
termination based on electrochemical detection without
chromatographic separation. Two electrochemical works
were carried out by differential pulse polarography [14,
15] and, in the others, a modified carbon paste electrode
was used [16, 17]. Due to similar structure of the PRA and
doxazosin, Arranz and co-authors also evaluated the ability
to pre-concentrate PRA on the Tenax-modified carbon
paste electrode [19]. However, the results showed that PRA
did not accumulate with time in this working electrode be-
cause there is not a benzodioxan moiety in your molecule,
which is involved in the adsorption between doxazosin and
Tenax. These electroanalytical studies can be still improved in
order to obtain a practical and efficient method for routine
analysis in pharmaceutical laboratories, eliminating the need
for modification, or use of electrodes with toxic potential (e.g.,
mercury). Furthermore, these methods can also improving the
analytical parameters by increasing reproducibility, simplicity,
and analytical frequency.
In this context, this work presents a new method for PRA
determination by flow injection analysis with multiple-pulse
amperometric detection (FIA-MPA), which may yield a
higher analytical frequency and greater electrochemical re-
sponse reproducibility when compared with stationary tech-
niques. It is worth noting that the MPA detection enables up to
10 potential pulses as a function of time and the acquisition of
up to 10 amperograms, independent, simultaneous which
brings a number of advantages over other methods such as
use of internal standard in flow systems [20], and for increas-
ing the selectivity of the electrochemical method for the de-
tection of the products of oxidation/reduction, even in the
presence of interfering species [21, 22] and also may enable
simultaneous analysis of electroactive compounds [23–26].
The use of boron-doped diamond (BDD) film electrode has
been widely used for analysis of other drugs in pharmaceutical
formulations [27–30] and is an excellent alternative in im-
proving the electrochemical response of PRA due to its high
stability and reproducibility. The BDD electrode also offers
several advantages including a broad potential window and
low background [31–37]. In these perspectives, this work
J Solid State Electrochem
presents a simple, fast, and reproducible analytical method
for PRA determination in pharmaceutical formulations and
of potential application in biological fluids by FIA-MPA using
BDD electrode.
Experimental
Reagents and solutions
The used reagents were of analytical grade, and all solutions
were prepared in deionized water with a resistivity of no less
than 18.2 MΩ cm obtained from the ELGA purification sys-
tem, Di-MKZ model. Initially, a stock solution of
1.0 × 10−3 mol L−1 PRA (Sigma-Aldrich, São Paulo, Brazil)
was prepared in water. This stock solution of PRA was diluted
in the following supporting electrolytes for studies of electro-
chemical detection: sulfuric acid from Vetec (Duque de
Caxias, Brazil); acetate buffer, acetic acid/sodium acetate from
Merck (Rio de Janeiro, Brazil); phosphate buffer, sodium
dihydrogen phosphate/sodium hydrogen phosphate from
Vetec (Duque de Caxias, Brazil); borate buffer, boric acid/
borate sodium from Merck (Rio de Janeiro, Brazil); all
supporting electrolytes were prepared at concentration of
0.1 mol L−1. The electrochemical response to analyte was
studied in a large range of pH using Britton-Robinson buffer
and the above electrolytes by cyclic voltammetry. A Britton-
Robinson buffer solution was composed of a mixture of
0.1 mol L−1 acetic acid, boric acid, and phosphoric acid, and
its different pH values were adjusted with sodium hydroxide.
The best conditions for determination of PRA by FIA-MPA
using BDD electrode were obtained in 0.1 mol L−1 phosphate
buffer (pH 4.0).
The interference studies in urine samples were carried out
with presence of the ascorbic acid and uric acid, both stan-
dards from Sigma-Aldrich (São Paulo, Brazil). Standards of
the interfering species were diluted in buffer phosphate solu-
tion at concentration of 1 to 1000 times higher than the analyte
concentration for evaluating interference of the PRA detection
by FIA-MPA. The human urine samples were collected from
one healthy patient and were diluted in phosphate buffer (pH
4.0) solution without any treatment for FIA-MPA detection.
The addition-recovery studies of PRA were carried out in
these urine samples.
The capsules of PRA, manufactured by Pfizer (Guarulhos,
Brazil) and marketed under trade name Minipress® SR, were
obtained containing 1.0 mg of active ingredient. The capsules
(20) of PRA were powdered in a mortar, and a weight corre-
sponding to one capsule was dissolved in electrolyte using an
ultrasonic bath for 30 min for the MPA-FIA detection or in
mobile phase for the HPLC-DAD detection. The sample and
standard solutions were filtered through a membrane filter
(pore size of 0.45 mm) before injection in the HPLC system.
J Solid State Electrochem
The addition-recovery studies of PRA were also carried out in
these pharmaceutical samples.
Instrumentation and apparatus
The electrochemical measurements (amperometric and
voltammetric) were performed using a Potentiostat from
Autolab (Eco Chemie, the Netherlands) model PGSTAT
128 N with GPES 4.9 software. An electrochemical flow cell
(Bwall jet^ type) with three-electrode was lab-made. A wire of
platinum and an Ag/AgCl with KCl saturated were used as
auxiliary and reference electrodes, respectively. The working
electrode was a thin film (ca.1.2 mm) of BDD (approximately
8000 ppm doping level) supported on a polycrystalline silicon
wafer (NeoCoat SA, La Chaux-de-Fonds, Switzerland). One
piece of BDD material (1.0 × 1.0 cm) was used in the flow
cell, and the electrode area was delimited by using a rubber O-
ring with 0.4 cm of diameter (electrode area = 0.13 cm2).
Background current correction was carried out using the
GPS software from Autolab. The electrochemical pretreat-
ment of the BDD electrode for PRA detection was evaluated
by cyclic voltammetry. The BDD electrode was anodically
pretreated in a 0.5mol L−1 H2SO4 solution by applying
0.001 A during 120 s. The cathodic pretreatment was carried
out by applying −0.03 A during 360 s using the same solution.
The BDD electrode was pretreated only once, prior to the
measurements.
The FIA system (single-line) was composed of polyethyl-
ene tubing with 0.5 mm internal diameter, an acrylic manual
injector and flow rate was controlled by the pressure generated
by a water column [38]. The flow rate and injection volume
were investigated in the range of 0.5 to 4.0 mL min−1 and 50
to 350 μL, respectively.
The comparison of the method proposed for PRA determi-
nation in pharmaceutical samples was performed by the offi-
cial method using HPLC-UV [4]. The HPLC system used in
this work was a Shimadzu (Kyoto, Japan). The column used
was C18 (10, 4.6, 5 mm) from Macherey-Nagel (Germany).
The mobile phase was composed of methanol/water (70:30)
with 1 % acetic acid (v/v). All HPLC analysis were carried out
at room temperature (30 °C) with an injection volume of
20 μL and a flow rate of 1.0 mL min−1 (isocratic), while
detection was performed at 254 nm.
Results and discussion
Electrochemical behavior of prazosin
The electrochemical behavior of PRA was studied by cyclic
voltammetry at BDD electrode in various electrolytes. The
0.1 mol L −1 phosphate buffer (pH 4.0) was chosen as
supporting electrolyte because it presented the best results
for sensitive and selective detection of PRA. After cathodic
and anodic electrochemical treatments applied to BDD elec-
trode, the electrochemical behavior of PRA was re-evaluated
in the supporting electrolyte. The cathodic treatment was
chosen due to its better definition of the reduction peak
observed for PRA. Therefore, all studies were performed
after cathodic electrochemical pretreatment of the working
electrode surface. In these conditions, the cyclic voltam-
mograms are presented in Fig. 2.
As can be seen in Fig. 2, there are two oxidation peaks
(0.97 and 1.40 V) and one reduction peak (−0.75 V) for
PRA on BDD electrode. The oxidation and reduction process-
es were described by Arranz and co-authors, which used a
carbon paste electrode modified with nafion [16]. These au-
thors observed at first scan just one oxidation process, which
posteriorly generated a quasi-reversible cathodic process.
Although it could not be confirmed by cyclic voltammetry at
BDD electrode that the reduction is a quasi-reversible electro-
chemical process, FIA-MPA confirmed that this reduction
process on BDD electrode presents similar electrochemical
behavior to carbon paste electrode modified.
The electrochemical mechanism elucidated in the literature
for PRA on carbon paste electrode proposes that the first ox-
idation current is controlled by adsorption of the analyte at the
electrode surface [16]. According to these authors, this anodic
process corresponds to the oxidation of the adsorbed species
of PRA, which can produce dimer compounds through the
oxidation of the amine group present in this molecule along
with a four-electron and four-proton transfer process. Thus,
the PRA oxidized form might be reduced by an azo group,
in an almost reversible process with two-electron and two-
proton transfer [16]. We suggest that the electrochemical
oxidation and reduction mechanism of the PRA on BDD
electrode is similar to verified on carbon paste electrode.
However, the first oxidation process should occur in two
steps on BDD electrode. Moreover, the plot of the current
for the oxidation peaks of PRA (0.97 and 1.40 V) as a
function of the root of the scan rate (10 to 500 mV s−1)
Fig. 2 Cyclic voltammograms on BDD electrode in 0.1 mol L−1
phosphate buffer pH 4.0 without (black line) and with addition of PRA
1.0 × 10−4 mol L −1 (red line). The scan was started at −1.0 V in the
positive direction. Scan rate 50 mV s −1

was linear, thus supporting that the oxidation processes are
controlled by diffusion.
As one of the purposes of this work is to determine the
PRA in urine, ascorbic acid (AA) and uric acid (UA) are
common interferents in this sample type due to overlapping
of their oxidation processes with of the analyte [39]. So, PRA
determination is not possible by application of anodic poten-
tial pulses in the MPA detection. However, as the AA and UA
do not exhibit reduction processes on the BDD electrode, the
PRA determination is possible by application of cathodic po-
tential pulse in the MPA detection without interference of
these compounds. Thus, the PRA firstly must be oxidized
in the generator potential pulse and quantified by the ap-
plication of a second potential pulse (collector) through the
reduction of the product generated at BDD electrode. Thus,
all optimization studies by FIA-MPA detection of this
work are given in function of the collector potential pulse.
Optimization parameters of FIA-MPA detection
Optimization parameters were performed for PRA determina-
tion in urine and pharmaceutical formulations by FIA-MPA.
The potential pulses as well as their application times were
optimized in function of the selectivity and sensitivity for
analyte quantification. These pulses were continuously ap-
plied in function of time (cyclical form) and the following
potential pulses were selected (amperograms shown in Fig. 3):
I) +1.6 V for 400 ms: PRA and common interferents as AA
e UA are oxidized, but only the electrochemical generated
product from PRA is electroactive in the cathodic region on
BDD electrode.
II) −1.0 V for 30 ms: the electrochemical generated product
from PRA in the oxidation step is reduced and quantified,
without the interference of AA and UA.
Fig. 3 Amperograms obtained by FIA-MPA detection in supporting
electrolyte with duplicate injections of solutions containing
10 μmol L−1 of only PRA, only UA, only AA and all together (PRA +
UA + AA) in the same concentration. Flow rate 3.0 mL min−1; injection
volume 150 μL. Potential pulses on BDD electrode 1.6 V/400 ms and
−1.0 V/30 ms
J Solid State Electrochem
Fig. 4 Repeatability data obtained from successive injections of a
solution containing 10 μmol L−1 (a) or 100 μmol L−1 (b) of PRA. Flow
rate 3.0 mL min−1; injection volume 150 μL. Supporting electrolyte
0.1 mol L −1 phosphate buffer pH 4.0. Potential pulses on BDD
electrode: 1.6 V/400 ms (not shown) and −1.0 V/30 ms
It is worth mentioning that was necessary the application of
more potential pulses between the potentials selected to de-
crease the capacitive current in the MPA detection due to the
high potential jump (2.6 V) over BDD electrode. To solve this
problem, the potential pulses of 0.8 V/100 ms and −0.2 V/
100 ms were selected, but the current signals obtained at these
potential pulses were not acquired, and the respective
amperograms are not shown in Fig. 3, as well as in other
figures in this work. The flow rate and sample loop volume
in the FIA system are also important to better efficiency of the
method [21]. So, these parameters were optimized based on
better analytical frequency, analytical response, and repeat-
ability for PRA determination. The best conditions were ob-
tained using 3.0 mL min−1 and 150 μL as flow rate and the
injection volume, respectively. In this condition, the analytical
frequency was estimated in 70 injections per h, which pro-
vides faster analysis than the other applications reported for
the determination of PRA.
Analytical parameters
The analytical parameters of the FIA-MPA method were eval-
uated (after optimization of the conditions) for PRA
Fig. 5 Amperogram obtained by FIA-MPA detection after triplicate in-
jections of standard solutions containing PRA at concentrations from 2 to
200 μmol L−1 (a–i) and the respective calibration curve is showed in the
inset. Other conditions, see Fig. 4
J Solid State Electrochem
Table 1 FIA-MPA responses
obtained after triplicate injections Concentration ratio of the
of solutions containing interfering substance
2.0 μmol L−1 PRA and increasing
concentrations of AA and UA 1 100.0
50
100
determination in pharmaceutical formulations and in human
urine. The stability study of the BDD electrode coupled to the
FIA system was evaluated by detection of PRA at collector
potential pulse (−1.0 V). The repeatability study (Fig. 4) was
performed by 10 successive injections of solutions containing
10 μmol L−1 PRA, then more 10 injections (with a concentra-
tion 10 times higher than before) and, finally, more 10 injec-
tions in the same initial concentration of PRA.
As can be noted in Fig. 4, even after the injections of high
PRA concentrations, the first 10 peaks did not differ signifi-
cantly from the last 10 measurements. The RSD for PRA
detection were 2.46 % for the first 10 peaks (Fig. 4a),
2.85 % for 10 injections at high concentrations (Fig. 4b) and
2.79 % for the last 10 peaks (Fig. 4a). These results demon-
strated that the FIA system using BDD electrode can present
high reproducibility for PRA quantification, mainly because
the phenomenon of working electrode contamination (or pas-
sivation) is practically absent due to inert surface of the BDD.
The amperometric responses for triplicate injections of so-
lutions containing increasing concentrations of PRA and the
respective calibration curve are presented in Fig. 5. The linear
working range was from 2 to 200 μmol L−1 with linear corre-
lation coefficient greater than 0.99. The linear regression
equation for PRA analysis in these conditions was
I(A) = 0.0936 (±0.0324) + 0.1531(±0.0043) c (mol L−1). The
detection limit was estimated at 0.5 μmol L−1. Although the
LOD value obtained for PRA by proposed method is higher
than some values reported by others methods, the FIA-MPA
detection provides enough sensibility for PRA determination
in pharmaceutical formulations, as well as in urine samples.
As advantages in relation to other methods, this work presents
a simpler and faster method using an unmodified working
electrode, offering a good alternative for routine analysis of
PRA in pharmaceutical samples and a potential application in
biological fluids.
As previously shown (Fig. 3), the AA and UA are not
interferents for PRA detection at collector potential pulse
Table 2 Quantity-control of the PRA in pharmaceutical formulation
obtained by the proposed method (FIA-MPA) and by official method
(HPLC-UV) and their respective values of standard deviation (n = 3)
Sample Ingredient Labeled (mg) FIA-MPA (mg) HPLC-UV (mg)
Capsules PRA 1.00 0.92 ± 0.06 0.96 ± 0.02
Current signal of PRA (%) Current signal of PRA (%)
for relation AA/PRA for relation UA/PRA
100.0
99.5 103.2
104.1 102.9
(−1.0 V). However, due to high concentrations of AA and
UA in urine samples, the concentration effect of these
interferents on current signal of analyte also was evaluated
(Table 1). As can be observed in Table 1, the current signal
of PRA was relatively constant in the presence of up to 100
times more of AA or UA. For higher concentrations of AA, a
decrease in the PRA signal was observed. The UA was not
soluble in the supporting electrolyte at higher concentrations,
and so, it did not interfere in the analysis of PRA.
The addition-recovery studies in pharmaceutical samples
were carried out to verify the performance of the proposed
method. The results obtained for recovery of PRA in formu-
lations pharmaceutical (n = 3) and human urine (n = 3) were
100.1 % (±1.0) and 98.0 % (±5.0), respectively. The values
obtained were close to 100 %, indicating the absence of matrix
effect in these samples.
The results obtained for the determination of PRA in phar-
maceutical samples using the proposed method versus the
official method (HPLC-UV) are presented in Table 2.
Statistical tests (F and t) were applied to results obtained by
both methods with a confidence level of 95 %. The calculated
values from the statistical tests were smaller than the tabulated
critical values, and thus the results can be considered similar
for both methods.
Conclusions
This paper presented a fast, simple and inexpensive method
for the determination of PRA in pharmaceutical formulations
using FIA-MPA detection with BBD electrode. Moreover, this
work demonstrated that an unmodified working electrode can
be used for selective determination of PRA in the presence of
ascorbic acid and uric acid (electroactive interfering com-
pounds), offering a good possibility to apply the proposed
method for the analysis of biological samples that contains
other species with electrochemical behavior similar to PRA.
Acknowledgments The authors are grateful to Conselho Nacional de
Desenvolvimento Científico e Tecnológico (CNPq – Project: 481683/
2013-5) and Fundação de Amparo à Pesquisa do Estado de Minas Gerais
(FAPEMIG) for financial support. This work is a collaboration research
project of members of the Rede Mineira de Química (RQ-MG) supported
by FAPEMIG (Project: CEX - RED-00010-14).

References
1. Hardman JG, Limbird LE (2006) Goodman & Gilman’s the phar-
macological basis therapeutics. McGraw Hill, New York
2. L.X. Yu and B.V. Li (eds.), (2014) FDA Bioequivalence Standards,
AAPS Advances in the Pharmaceutical Sciences. Series 13, doi:10.
1007/978-1-4939-1252-0. Springer, New York
3. British Pharmacopoeia (1988) Vols. I and II, by Great Britain,
British Pharmacopoeia Commission Publisher: London HMSO
1988, Description: xli, 1575p
4. Healthwise Knowledgebase (1998) US Pharmacopeia, Rockville.
http://www.healthwise.org . Accessed 21 Sept 2015
5. Batchman WJ (1986) High Performance liquid chromatographic
determination of diuretic-antihypertensive combination products.
I. Prazosin and polythiazide. J Liq Chromatogr 9(5):1033–1049
6. Sultana N, Saeed Arayne M, Shah SN (2014) Development and
validation for the simultaneous quantification of prazosin,
amlodipine, diltiazem and verapamil in API, dosage formulation
and human serum by RP-HPLC: application to in vitro interaction
studies. Med Chem 4(12):770–777
7. Yee YG, Rubin PC, Meffin P (1979) Prazosin determination by
high-pressure liquid chromatography using flourescence detection.
J Chromatogr A 172(1):313–318, 21 April 1979
8. Fletcher AJ, Addison RS, Mortimer RH, Cannell GR (1995) Rapid
determination of prazosin in perfusion media by HPLC with solid
phase extraction. J Liq Chromatogr 18(14):2911–2923. doi:10.
1080/10826079508009334
9. Li PA, Peng H, Peng DJ, Zhou MQ, Zhang J (2015) Rayleigh light
scattering detection of three α1-adrenoceptor antagonists coupled
with high performance liquid chromatograph. Spectrochim Acta A
Mol Biomol Spectrosc 147:178–184, 5 August 2015
10. Rathinavelu A, Malave A (1995) High-performance liquid chroma-
tography using electrochemical detection for the determination of
prazosin in biological samples. J Chromatogr B Biomed Sci Appl
670(1):177–182, 4 August 1995
11. Sreedhar K, Sastry CSP, Reddy MN, Sankar DG (1996)
Spectrophotometric methods for the determination of prazosin hy-
drochloride in tablets. Talanta 43(11):1847–1855
12. Daldrup T, Susanto F, Michalke P, Fresenius Z (1981) Kombination
yon DC, GC (OV 1 und OV 17) und HPLC (RP 18) zur schnellen
Erkennung von Arzneimitteln, Rauschmitteln und verwandten
Verbindungen. Fresenius Z Anal Chem 308:413–427
13. Soini H, Riekkola ML, Novatny MV (1994) Mixed polymer net-
works in the direct analysis of pharmaceuticals in urine by capillary
electrophoresis. J Chromatogr A 680(2):62–634, 7 October 1994
14. Altiokka G, Tuncel M (1997) Differential pulse polarographic de-
termination of prazosin hydrochloride in tablets. Die Pharmazie
[0031–7144] Altiokka, G 52(5):401–402
15. Özgür MÜ, Aycan S, Islimyeli S (1995) Differential pulse polaro-
graphic determination of prazosin hydrochloride in tablets. Die
Pharm 50(6):435–436
16. Arranz A, de Betoño SF, Echevarria C, Moreda JM, Cid A, Valentín
JFA (1999) Voltammetric and spectrophotometric techniques for
the determination of the antihypertensive drug Prazosin in urine
and formulations. J Pharm Biomed Anal 21:797–807
17. Arranz A, Moreda JM, Arranz JF (2000) Anodic stripping
voltammetric assay for the determination of prazosin at carbon
paste electrodes. Química Analítica [0212–0569] Arranz, A
19(1):31–37
18. Uslu B, Ozkan AS (2011) Electroanalytical methods for the deter-
mination of pharmaceuticals: a review of recent trends and devel-
opments. Anal Lett 44(16):2644–2702
19. Arranz A, de Betoño SF, Moreda JM, Cid A, Arranz JF (1997)
Cathodic stripping voltammetric determination of doxazosin in
J Solid State Electrochem
urine and pharmaceutical tablets using. Carbon paste electrodes.
Analyst 122(8):849–854
20. Gimenes DT, Santos WTP, Muñoz RAA, Richter EM (2010)
Internal standard in flow injection analysis with amperometric de-
tection. Electrochem Commun 12(2):216–218
21. dos Santos WTP, Gimenes DT, Richter EM, Angnes L (2011) Flow
injection analysis with multiple pulse amperometric detection: po-
tentialities and applications. Quim Nova 34(10):1753–1761
22. Gimenes DF, dos Santos WTP, Tormin TF, Muñoz RAA, Ricther
EM (2010) Flow-injection amperometric method for indirect deter-
mination of dopamine in the presence of a large excess of ascorbic
acid. Electroanalysis 22(1):74–78
23. Pereira PF, Marra MC, Lima AB, dos Santos WTP, Muñoz RAA,
Richter EM (2013) Fast and simultaneous determination of
nimesulide and paracetamol by batch injection analysis with am-
perometric detection on bare boron-doped diamond electrode.
Diam Relat Mater 39:41–46. doi:10.1016/j.diamond.2013.07.010
24. Medeiros RA, Lourencao BC, Rocha-Filho RC, Fatibello-Filho O
(2010) Simple flow injection analysis system for simultaneous de-
termination of phenolic antioxidants with multiple pulse ampero-
metric detection at a boron-doped diamond electrode. Anal Chem
82(20):8658–8663. doi:10.1021/ac101921f
25. Chaves SC, Aguiar PNC, Torres LMFC, Gil ES, Luz RCS, Damos
FS, Munoz RAA, Richter EM, dos Santos WTP (2015)
Simultaneous determination of caffeine, ibuprofen, and paraceta-
mol by flow-injection analysis with multiple-pulse amperometric
detection on boron-doped diamond electrode. Electroanalysis
27(12):2785–2791. doi:10.1002/elan.201500306
26. dos Santos WTP, Almeida EGN, Ferreira HEA, Gimenes DF,
Richter EM (2008) Simultaneous flow injection analysis of para-
cetamol and ascorbic acid with multiple pulse amperometric detec-
tion. Electroanalysis 20(17):1878–1883. doi:10.1002/elan.
200804262
27. Faria EO, Lopes-Junior ACV, Souto DEP, Leite FRF, Damos FS,
Luz RCS, Santos AS, Franco DL, dos Santos WTP (2012)
Simultaneous determination of caffeine and acetylsalicylic acid in
pharmaceutical formulations using a boron-doped diamond film
electrode by differential pulse voltammetry. Electroanalysis 24(5):
1141–1146. doi:10.1002/elan.201500306
28. Sartori ER, Medeiros RA, Rocha-Filho RC, Fatibello-Filho O
(2010) Square-wave voltammetric determination of propranolol
and atenolol in pharmaceuticals using a borondoped diamond elec-
trode. Talanta 81(4–5):1418–1424. doi:10.1016/j.talanta.2010.02.
046
29. Santos MCG, Tarley CRT, Dall’Antonia LH, Sartori ER (2013)
Evaluation of boron-doped diamond electrode for simultaneous
voltammetric determination of hydrochlorothiazide and losartan in
pharmaceutical formulations. Sensors Actuators B Chem 188:263–
270. doi:10.1016/j.snb.2013.07.025
30. Lima AB, Torres LMFC, Guimaraes CFRC, Verly RM, da Silva
LM, Carvalho-Junior AD, dos Santos WTP (2014) Simultaneous
determination of paracetamol and ibuprofen in pharmaceutical sam-
ples by differential pulse voltammetry using a boron-doped dia-
mond electrode. J Braz Chem Soc 25(3):478–483. doi:10.5935/
0103-5053.20140005
31. Macpherson JV (2015) A practical guide to using boron doped
diamond in electrochemical research. Phys Chem Chem Phys
17(5):2935–2949. doi:10.1039/C4CP04022H
32. Einaga Y, Foord JS, Swain GM (2014) Diamond electrodes: diver-
sity and maturity. Mater Res Bull 39(6):525–532. doi:10.1557/mrs.
2014.94
33. Pleskov YV (2000) Synthetic diamond, a New electrode material
for electroanalysis. J Anal Chem 55(11):1045–1050, Translated
from Zhurnal Analificheskoi Khimii, Vol. 55, No. I1, 2000, pp.
1165–1171
J Solid State Electrochem
34. Suffredini HB, Pedrosa VA, Codognoto L, Machado SAS, Rocha-
Filho RC, Avaca LA (2004) Enhanced electrochemical response of
boron-doped diamond electrodes brought on by a cathodic surface
pre-treatment. Electrochim Acta 49(22–23):4021–4026. doi:10.
1016/j.electacta.2004.01.082
35. Chailapakul O, Siangproh W, Tryk DA (2006) Boron-doped dia-
mond-based sensors: a review. Sens Lett 4(2):99–119. doi:10.1166/
sl.2006.008
36. Luong JHT, Male KB, Glennon JD (2009) Boron-doped diamond
electrode: synthesis, characterization, functionalization and analyt-
ical applications. Analyst 134(10):1965–1979. doi:10.1039/
B910206J
37. Peckova K, Musilova J, Barek J (2009) Boron-doped diamond film
electrodes—New tool for voltammetric determination of organic
substances. Crit Rev Anal Chem 39(3):148–172. doi:10.1080/
10408340903011812
38. dos Santos WTP, Ceolin MP, Albuquerque YDT, Richter EM
(2007) The use of pressure generated by a water column to control
flow rates in flow analysis systems. Quim Nova 30(7):1754–1758
39. Dey RD, Gupta S, Paira R, Chen SM, Raj CR (2012) Flow
injection amperometric sensing of uric acid and ascorbic acid
using the self-assembly of heterocyclic thiol on Au elec-
trode. J Solid State Electrochem 16(1):173–178. doi:10.
1007/s10008-011-1311-1