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Physical Chemistry 2012, 2(1): 6-11
DOI: 10.5923/j.pc.20120201.02
Development and Validation of the Quantitative Analysis
of Ceftazidime in Powder for Injection by Infrared
Spectroscopy#
Andréia de Haro Moreno, Hérida Regina Nunes Salgado*
Department of Drugs and Medicines, School of Pharmaceutical Sciences, University of São Paulo State, Araraquara, 14801-902, Brazil
# Dedicated to Faculdade de Ciências Farmacêuticas - Universidade Estadual Paulista (UNESP) on the occasion of its 88th anniversary
Abstract Ceftazidime quantification by the infrared spectroscopy was developed and validated for pharmaceutical
preparations in powder for injection. This method involved absorbance measurements of the band corresponding to aro-
matic ring centered by 1475-1600 cm-1. Selectivity, linearity, precision and accuracy were determined in order to validate
the proposed method. It was also found that the excipient did not interfere with the assay. Calibration curve was obtained
for ceftazidime at 0.5 to 7.0 mg, and mean recovery percentage was 98.98 ± 0.70. The proposed method was successfully
applied to the assay of ceftazidime in powder for injection.
Keywords Ceftazidime, Infrared, Spectroscopy, Quantitative, Determination
1. Introduction
Ceftazidime (Fig. 1) is a third-generation cephalosporin
that is widely used for the treatment of serious infections
caused by Gram-negative bacteria, including Pseudomonas
aeruginosa. They include biliary-tract infections, bone and
joint infections, cystic fibrosis (respiratory-tract infections),
endophthalmitis, infections in immunocompromised pa-
tients (neutropenic patients), meningitis, peritonitis, pneu-
monia, septicaemia, skin infections (including burns, ul-
ceration) and urinary-tract infections[1-13].
Figure 1. Chemical structure of ceftazidime – C22H22N6O7S2 (mw
546.58)
Ceftazidime is administrated by slow intravenous
* Corresponding author:
salgadoh@fcfar.unesp.br (Hérida Regina Nunes Salgado)
Published online at http://journal.sapub.org/pc
Copyright © 2012 Scientific & Academic Publishing. All Rights Reserved
infusion over 24 hours. The infusion solutions are prepared
in advance and stored in the pharmacy[11,14].
Several analytical procedures are available in the litera
ture for the analysis of cephalosporins. These methods in-
cluded spectrophotometry[15-24], high performance liquid
chromatography[2,9,25-29], capillary eletrophoresis[30],
fluorimetry[31-35], polarography[36-40] and titrimetry[41].
Infrared spectroscopy is an important technique used for
the characterization of very complex mixtures. The portion
of the infrared region most useful for analysis of organic
compounds is that having a wavelength range from 2500 to
16000 nm[42].
Infrared spectroscopy exploits the fact that molecules
have specific frequencies at which they rotate or vibrate
corresponding to discrete energy levels (vibrational modes).
These resonant frequencies are determined by the shape of
the molecular potential energy surfaces, the masses of the
atoms and by the associated vibronic coupling. In order to a
vibrational mode in a molecule to be infrared active, it must
be associated with changes in the permanent dipole. Never-
theless, resonant frequencies can be in a first approach re-
lated to the strength of the bond, and the mass of the atoms
at either end of it. Thus, the frequency of vibrations can be
associated with a particular bond type[43].
Infrared spectrum of a sample may be obtained by pass-
ing a beam of infrared light through the sample. Examina-
tion of the transmitted light reveals how much energy was
absorbed at each wavelength. This can be done with a
monochromatic beam, which changes in wavelength over
time, or by using a Fourier transform instrument to measure
Physical Chemistry 2012, 2(1): 6-11 7
all wavelengths at once. From this, a transmittance or ab-
sorbance spectrum can be produced, showing at which in-
frared wavelengths the sample absorbs. Analysis of these
absorption characteristics reveals details about the molecu-
lar structure of the sample[44].
Infrared spectroscopy is widely used in both research and
industry as a simple and reliable technique for measurement,
quality control and dynamic measurement. It is especially
used to forensic analysis in both criminal and civil cases
and has been highly successfully for applications in both
organic and inorganic chemistry[45].
Although the infrared spectroscopy is officially accepted
to identification of several compounds, the literature shows
few publications that employ this method for the quantita-
tive analysis[46].
Recently, Moreno and Salgado published four methods
for the analysis of ceftazidime in powder for injection:
microbiological assay[47], high performance liquid chro-
matography[48] and spectrophotometry[49,50]. Therefore,
the aim of this study was developed and validated a new
and unpublished infrared spectroscopic method for quanti-
tative determination of ceftazidime in powder for injec-
tion.].
2. Material and Methods
2.1. Chemicals
Ceftazidime reference substance (assigned purity 99.98%)
and ceftazidime powder for injection were kindly supplied
by Ariston Química e Farmacêutica Ltda. (São Paulo, Brazil).
Ceftazidime powder for injection (Ceftazidon) was
claimed to contain 1000 mg (as anhydrous base) of the drug
and 118 mg of anhydrous sodium carbonate as excipient
(solubilizer).
Potassium bromide (Merck, Darmstadt, Germany) used to
the preparation of translucent pellets was of analytical grade
and was previously dried at 120ºC for 2 h.
2.2. Instrumentation and Analytical Conditions
2.2.1. Equipment
A conventional SHIMADZU IR Spectrometer Model
FTIR 8300 (Tokyo, JP) with spectral digitalization was used
for obtaining data and respective absorption regions (wave-
length region of 500-4000 cm-1 at 2 cm-1 intervals).
2.2.2. Obtaining of Analytical Curve
Translucent pellets were prepared by dilution of cef-
tazidime reference substance in potassium bromide to obtain
250 mg of total weight. Amounts of 0.5, 1.0, 2.0, 5.0 and 7.0
mg of ceftazidime reference substance (previously diluted
with potassium bromide 1:10, w/w) were prepared using
sufficient amount of potassium bromide to obtain 250 mg.
Powders were mixed and ground until the obtaining an ho-
mogeneous powder; so, this powder mixture was crushed in
a mechanical die press to form translucent pellets through
which the beam of the spectrometer can pass.
2.2.3. Sample Preparation
Twenty flasks containing ceftazidime powder for injection
were weighed and the average weight was determined. An
amount of powder equivalent to 300 mg of ceftazidime was
mixed and ground with potassium bromide for the obtaining
the homogeneous powder (1:10, w/w dilution). Dilutions
with potassium bromide were made to give final concentra-
tions of 3.0 mg in each translucent pellet. This dilution pro-
cedure was performed in triplicate. Lectures were made at
wavelength region of 500-4000 cm-1 and the absorbance
measurements were monitored at 1475-1600 cm-1 region,
that corresponding to the aromatic ring absorption region of
the molecule.
2.2.4. Sample Preparation
Sample concentrations (mg) were calculated by following:
CS =[AS x CRS] / ARS, where CS is the sample concentra-
tion (mg), CRS is the reference substance concentration (mg),
AS is the sample absorbance measurement and ARS is the
reference substance absorbance measurement.
2.2.5. Method Validation
The developed method was validated by the following
parameters: linearity, precision and accuracy as per ICH
Guidelines[51] and AOAC[52].
a) Linearity: To assays linearity of the method, doses of
reference substance were evaluated on 3 different days.
Regression lines were calculated by the least-squares method.
Statistical evaluation was made by ANOVA. For the infrared
spectrometric method, linearity was verified by analysis of 5
points at concentration range 0.5-7.0 mg.
b) Precision: Repeatability (intraday) and intermediate
precision (inter-day) were evaluated by the assay of 6 inde-
pendent samples in a day, under the same experimental
condition (standard and sample preparation as described
above). Results obtained on 3 different days were compared.
c) Accuracy: This parameter was determined by the re-
covery study, comparing theoretical and measured concen-
trations of ceftazidime reference substance added at the
beginning of the process. Translucent pellets were prepared
at concentration 3.0 mg in each pellet. Amounts of 30.0 mg
of ceftazidime sample dilution (1:10, w/w) in potassium
bromide and amounts of 15.0, 30.0 and 60.0 mg of cef-
tazidime reference substance, previously diluted in potas-
sium bromide (1:100, w/w), corresponding to 150, 300 and
600 µg of ceftazidime, respectively, were weighed, mixed
and ground with sufficient amount of potassium bromide for
the obtaining the homogeneous powder (250 mg each pellet),
giving final concentrations of 3.15, 3.30 and 3.60 mg in each
pellet, respectively, which correspond to 105, 110 and 120%
(R1, R2 and R3) of nominal analytical concentration. Each
level was made in triplicate.
Recovery percentage of ceftazidime added was calculated
8 Andréia de Haro Moreno et al.: Development and Validation of the Quantitative Analysis
of Ceftazidime in Powder for Injection by Infrared Spectroscopy
using the equation proposed by AOAC[52].
3. Results and Discussion
Quality control is very important to guarantee the safety
and the effectiveness of pharmaceuticals. In order to control
the production line as best as possible and to increase the
productivity a lot of samples were drawn and analysed in
certain intervals. But still the test procedure solely rely on
random testing, because it was up to now the only way to
assure the quality of the millions of products produced in a
day. Clusters of products, faulty in constituents, concentra-
tion or humidity, caused by momentary production problems
could not always be detected[53].
Near-infrared spectroscopy is a widely recognized tech-
nique for identification and verification of compounds. It is
non-contact, non-destructive and no sample preparation is
required[54]. This technique has been used to identify sev-
eral compounds, such as pharmaceuticals, cosmetics and
foods, but requires expensive equipments and mathematical
pre-treatments[54, 55, 56]. So, the aim of this study was
developed an infrared spectrometric method for the deter-
mination of ceftazidime in powder for injection.
Infrared spectra obtained presented characteristic absorp-
tion bands of cephalosporin compounds, such as 3660-3250
cm-1 (N-H group axial deformation), 1750-1725 cm-1 (car-
boxylic acid function C=O stretching), 1475-1600 cm-1
(aromatic ring C=C axial deformation), 1350-1300 cm-1
(C-N axial deformation) and 1680-1630 cm-1 (amide group
C=O axial deformation), according to Figure 2.
Spectra showed characteristic absorption bands and ab-
sorbance measurements of them; so, it was possible to verify
the linear relationship between ceftazidime concentrations
and absorbance measurements when different amounts of the
drug were used to prepare the translucent pellets. Spectra
were analysed and compared to that obtained of ceftazidime
reference substance for identify the sample. Absorption
bands of aromatic ring were chosen for absorbance moni-
toring because those absorption bands did not occur in ex-
cipient present in pharmaceutical preparations (anhydrous
sodium carbonate or arginine).
Infrared spectroscopic method presented many advantages
when compared to both UV/Vis spectrophotometric methods:
there wasn’t necessary to realize extraction stages, which
reduced time analysis and costs with filter equipments and
membranes. Besides, drugs presenting solubility problems
with more appropriate solvent could be prepared in powder
form (generally, potassium bromide) for obtaining the pellets.
Time procedure was also smaller than that solutions prepa-
ration.
Excipients present in pharmaceutical preparation (powder
for injection) did not interfere with the results obtained be-
cause those do not present specific absorption bands used to
identify and quantify the analysed drug.
Despite being only moderately selective, infrared spec-
troscopic method was a very robust, easy and inexpensive
method when compared to other instrumental methods, of-
fering good precision in quantitative analysis.
Calibration curve of ceftazidime was obtained by plotting
absorbance measurements against drug concentration. The
curve was linear at range 0.5-7.0 mg, with a regression co-
efficient of 0.9998 and a linear regression equation of y =
0.1717x + 0.2129 (Figure 3).
Figure 2. Infrared spectrum for ceftazidime reference substance
Physical Chemistry 2012, 2(1): 6-11 9
Figure 3. Calibration curve for ceftazidime by infrared spectroscopic
proposed method
Results obtained through the infrared spectroscopic
method for ceftazidime powder for injection are displayed in
Table 1, which shows mean, e.p.m. and R.S.D. values.
Quantities of the drug found were in accordance with the
values claimed by the manufacturer (99.41%), indicating the
applicability of the proposed method to pharmaceutical
analysis. This method showed good precision, with R.S.D.
value found to be less than 2% (1.61%). There was no evi-
dence of interference from the excipient (anhydrous sodium
carbonate).
Tab l e 1. Experimental values obtained for the determination of ceftazi-
dime by the infrared spectroscopic proposed method
Accuracy may be expressed as percent recovery by the
assay of known added amounts of analyte[51-52]. Results
obtained from recovery test of ceftazidime are shown in
Table 2. The mean absolute recovery test was found to be
98.98%, indicating a good accuracy and the agreement with
spiked amount of reference substance.
Tab le 2 . Experimental values obtained in the recovery test for ceftazidime
by infrared spectroscopic proposed method
3. Conclusions
Ceftazidime quantification in powder for injection by the
infrared spectroscopic method demonstrated good linearity,
precision and accuracy at concentrations ranging from 0.5 to
7.0 mg. The present investigation showed that infrared
analysis could be also employed for quantitative determina-
tion of ceftazidime in pharmaceutical preparations, with
possible application for quantification of other drugs.
Therefore, it was an acceptable alternative method for the
routine quality control of ceftazidime in raw material and
pharmaceuticals. The proposed method used simple reagents,
with minimum sample preparation procedures, encouraging
its application in routine analysis.
ACKNOWLEDGEMENTS
Authors thank Ariston Química e Farmacêutica Ltda. (São
Paulo, Brasil) for providing ceftazidime reference substance
and ceftazidime powder for injection. This work was sup-
ported by PACD-FCFAr-UNESP-Brazil, FUNDUNESP-
Brazil, FAPESP-Brazil and CNPq-Brazil.
REFERENCES
[1] J.G. Hardman and L.E. Limbird, The Pharmacological Basis
of Therapeutics, New York, NY: McGraw-Hill Book Co.,
2006
[2] Baskaran, N.D., Gan, G.G., Adeeba, K., Sam, I.C., 2007,
Bacteremia in patients with febrile neutropenia after chemo-
therapy at a university medical center in Malaysia, Int. J. In-
fect. Dis., 23, 115-121
[3] Cavallo, J.D., Hocquet, D., Plesiat, P., Fabre, R., Rous-
sel-Delvallez, M., 2007, Susceptibility of Pseudomonas ae-
ruginosa to antimicrobials: a 2004 French multicentre hos-
pital study, J. Antimicrob. Agents Chemother., 59, 1021-1024
[4] Claridge, J.A., Edwards, N.M., Swanson, J., Fabian, T.C.,
Weinberg, J.A., Wood, C., Croce, M.A., 2007, Aerosolized
ceftazidime prophylaxis against ventilator-associated pneu-
monia in high-risk trauma patients: results of a double-blind
y = 0,1717x + 0,2129
R
2
= 0,9998
0
0,5
1
1,5
02468
Concentration (mg)
Absorbance
10 Andréia de Haro Moreno et al.: Development and Validation of the Quantitative Analysis
of Ceftazidime in Powder for Injection by Infrared Spectroscopy
randomized study, Surg. Infect. (Larchmt), 8, 83-90
[5] Eagye, K.J., Kuti, J.L., Nicolau, D.P., 2007, Evaluating em-
piric treatment options for secondary peritonitis using phar-
macodynamic profiling, Surg. Infect. (Larchmt), 8, 215-226
[6] Martin, M.G., 2007, Encephalopathy with myoclonic jerks
resulting from ceftazidime therapy: an under-recognized po-
tential side-effect when treating febrile neutropenia, Leuk.
Lymphoma, 48, 413-414
[7] Raja, N.S., 2007, Antimicrobial susceptibility pattern of
clinical isolates of Pseudomonas aeruginosa in a tertiary care
hospital, J. Microbiol. Immunol. Infect., 40, 178-82
[8] Rodenas, V., Garcia, M.S., Sanchez-Pedreno, C., Albero,
M.I., 1997, Spectrophotometric methods for the determina-
tion of cephradine or ceftazidime in human urine using batch
and flow-injection procedures, J. Pharm. Biomed. Anal., 15,
1687-1693.
[9] Adamis, G., Papaioannou, M.G., Giamarellos-Bourboulis,
E.J., Gargalianos, P., Kosmidis, J., Giamarellou, H., 2004,
Pharmacokinetic interactions of ceftazidime, imiprenem and
aztreonam with amikacin in healthy volunteers, Int. J. Anti-
microb. Agents, 23, 144-149
[10] A.R. Gennaro, Remington: The Science And Practice of
Pharmacy, 20th ed., Rio de Janeiro, Brazil: Guanabara Koogan,
2004
[11] Martindale, The Complete Drug Reference, London, England:
Pharmaceutical Press, 2005
[12] Myers, C.M., and Blumer, J.L., 1983, Determination of cef-
tazidime in biological fluids by using high-pressure liquid
chromatography, Antimicrob. Agents Chemother., 24,
343-346
[13] Arséne, M., Favetta, P., Favier, B., Bureau, J., 2002, Com-
parison of ceftazidime degradation in glass bottles and plastic
bags under various conditions, J. Clin. Pharm.Therap., 27,
205-209
[14] A. Korolkovas, Dicionário Terapêutico Guanabara, Rio de
Janeiro, Brazil: Guanabara Koogan, 2000
[15] Abdel-Khalek, M.M., and Mahrous, M.S., 1984, Use of
ammonium molybdate in the colorimetric assay of cepha-
losporins, Talanta, 31, 635-637
[16] Navarro, P.G., and Las Parras, P.M., 1991, Reaction of so-
dium amoxicillin with Cu(II) ion in a methanolic medium, J.
Pharm. Sci., 80, 904-907
[17] Zuhri, A.Z.A., Rady, A.H., El-Shahawi, M.S., Al-Dhaheri, S.,
1994, Spectrophotometric determination of ampicillin by
ternary complex formation with 1,10-phenantroline and
copper(II), Microchem. J., 50, 111-115
[18] Ayad, M.M., Shalaby, A.A., Abdellatef, H.E., Elsaid, H.M.,
1999, Spectrophotometric determination of certain cepha-
losporins through oxidation with cerium (IV) and
1-chlorobenzotriazole, J. Pharm. Biomed. Anal., 20, 557-564
[19] Al-Momani, I.F., 2001, Spectrophotometric determination of
selected cephalosporins in drug formulations using flow in-
jection analysis, J. Pharm. Biomed. Anal., 25, 751-757
[20] Mohamed, G.G., 2001, Spectrophotometric determination of
ampicillin, dicluxacillin, flucoxacillin and amoxicillin anti-
biotic drugs: ion-pair formation with molybdenum and thi-
ocyanate, J. Pharm. Biomed. Anal., 24, 561-567
[21] Martinez, L.G., Falco, P.C., Cabeza, A.S., 2002, Comparison
of several methods used for the determination of cephalos-
porins. Analysis of cephalexin in pharmaceutical samples, J.
Pharm. Biomed. Anal., 29, 405-423
[22] Salem, H., and Askal, H., 2002, Colourimetric and AAS
determination of cephalosporins using Reineck’s salt, J.
Pharm. Biomed. Anal., 29, 347-354
[23] El-Mammly, M.Y., 2003, Spectrophotometric determination
of flucoxacillin in pharmaceutical preparations some nitro-
phenols as a complexing agent, Spectrochim. Acta, 59,
771-776
[24] Amin, A.S., and Ragab, G.H., 2004, Spectrophotometric
determination of certain cephalosporins in pure form and in
pharmaceutical formulations, Spectrochim. Acta, 60,
2831-2835
[25] Nascimento, J.W.L., Omosako, C.E., Carmona, M.J., Auler
Junior, J.O., Santos, S.R.C.J., 2003, Micrométodo para
quantificação de cefuroxima em plasma através da
cromatografia líquida de alta eficiência. Aplicação na
profilaxia de pacientes submetidos à cirurgia cardíaca. Br. J.
Pharm. Sci., 39, 265-272
[26] Joshi, S., 2002, HPLC separation of antibiotics present in
formulated and unformulated samples, J. Pharm. Biomed.
Anal., 28, 795-809
[27] Samanidou, V.F., Hapeshi, E.A., Papadoyannis, I.N., 2003,
Rapid and sensitive high-performance liquid chromato-
graphic determination of four cephalosporins antibiotics in
pharmaceuticals and body fluids, J. Chromatogr. B, 788,
147-158
[28] Zajac, M., Jelinska, A., Dobrowolski, L., Oszczapowicz, I.,
2003, Evaluation of stability of cefuroxime in solid state, J.
Pharm. Biomed. Anal., 32, 1181-1187
[29] Zivanovic, L., Ivanovic, I., Vladimirov, S., Zecevic, M., 2004,
Investigation of chromatographic conditions for the separa-
tion of cefuroxime axetil and its geometric isomer, J. Chro-
matogr. B, 800, 175-179
[30] Castaneda, P.G., Julien, E., Fabra, H., 1996, Cross validation
of capillary electrophoresis and high-performance liquid
chromatography for cefotaxime and related impurities, J.
Chromatogr., 42, 159-164
[31] Fabre, H., Blanchin, M.D., Lerner, D., Mandrou, B., 1985,
Determination of cephalosporins utilizing thin-layer chro-
matography with fluorescence detection, Analyst, 110, 775
[32] Korany, M.A., El-Sayed, H.M.A., Galal, S.M., 1989, The
applications of a new chromogenic and fluorescent reagent
for cobalt(II), Anal. Lett., 22, 619-622
[33] Farrell, C.D., Rowell, F.J., Cumming, R.H., 1995, A rapid
fluorescence ELISA for ceftazidime, Anal. Proc., 32, 205-206
[34] Aly, F.A., Hefnawy, M.M., Belal, F., 1996, A selective
spectro-fluorimetric method for the determination of cepha-
losporins in biological fluids, Anal. Lett., 29, 1
[35] Yang, J.H., Zhou, G.J., Jie, N.Q., Han, R.J., Lin, C.G., Hu,
J.T., 1996, Simultaneous determination of cephalexin and
cephadroxil by using the coupling technique of synchronous
Physical Chemistry 2012, 2(1): 6-11 11
fluorimetry and H-point standard additions method, Anal.
Chim. Acta, 325, 195-200
[36] Sengun, F.I., Ulas, K., Fedai, I., 1985, Analytical investiga-
tions of cephalosporins-II. Polarographic behaviour of cef-
triaxone, cefuroxime, cefotaxime and ceftizoxime and assay
of their formulations, J. Pharm. Biomed. Anal., 3, 191-199
[37] Altinoz, S., Ozer, D., Temizer, A., Yuksel, N., 1994, Deter-
mination of ceftriaxone in aqueous humour and serum sam-
ples by differential-pulse adsorptive stripping voltametry,
Analyst, 119, 1575-1577
[38] El-Maali, N.A., Ali, A.M.M., Ghandour, M.A., 1994,
Square-wave voltametric determination of cefoperazone in a
bacterial culture, pharmaceutical drug, milk and urine, Elec-
troanalysis, 52, 599-604
[39] Reddy, G.V.S., and Reddy, S.J., 1997, Estimation of cepha-
losporin antibiotics by differential pulse polarography, Ta-
lanta, 44, 627-631
[40] Ozkan, S.A., Erk, N., Uslu, B., Ylmaz, N., Biryol, I., 2000,
Study on electrooxidation of cephadroxil monohydrate and its
determination by differential pulse voltametry, J. Pharm.
Biomed. Anal., 23, 263-273
[41] Fogg, A.G., Abadía, M.A., Henriques, H.P., 1982, Titrimetric
determination of the yield of sulphide formed by alkaline
degradation of cephalosporins, Analyst, 107, 449
[42] L. Ohannesian and A.J. Streeter, Handbook of Pharmaceuti-
cal Analysis, New York, NY: Marcel Dekker, 2002
[43] D. Harris, Análise Química Quantitativa, Rio de Janeiro,
Brazil: LTC Livros Técnicos e Científicos, 2001
[44] G.H. Jeffrey, J. Basset, J. Mendham, R.C. Denney, Vogel:
Análise Química Quantitativa, Rio de Janeiro, Brazil: LTC
Livros Técnicos e Científicos, 1992
[45] J.A. Barnard and R. Chayen, Metodos Modernos de Analisis
Quimico, Bilbao, Spanish: Bilbao, 1970
[46] Matkovic, S.R., Valle, G.M., Galle, M., Briand, L.E., 2001,
Desarollo y validación del análisis cuantitativo de ibuprofeno
en comprimidos por espectroscopia infrarroja, Acta Farm.
Bonaerense, 24, 561-567
[47] Moreno, A.H., and Salgado, H.R.N., 2007, Microbiological
assay for ceftazidime injection, J. AOAC Int., 90, 1379-1382
[48] Moreno, A.H., and Salgado, H.R.N., 2008, Development of a
new high-performance liquid chromatographic method for the
determination of ceftazidime, J. AOAC Int., 91, 739-743
[49] Moreno, A.H., and Salgado, H.R.N., 2008, Spectrophotome-
tric determination of ceftazidime in pharmaceutical prepara-
tions using neocuproin as a complexing agent, Anal. Lett., 41,
2143-2152
[50] Moreno, A.H., and Salgado, H.R.N., 2009, Rapid and selec-
tive UV spectrophotometric method for the analysis of cef-
tazidime, J. AOAC Int., 92, 820-824
[51] Validation of analytical procedures: text and methodology
Q2(R1)-ICH harmonized tripartite guideline, in: International
Conference on Harmonization of Technical Requirements for
Registration of Pharmaceuticals for Human Use, 2005
[52] Official Methods of Analysis, 17th ed., Gaithersburg, MD:
AOAC International, 2000
[53] D.G. Watson, Pharmaceutical Analysis, London, England:
Churchill Livingstone, 1999
[54] Herkert, T., Prinz, H., Kovar, K.A., 2001, One hundred per-
cent online identity check of pharmaceutical products by
near-infrared spectroscopy on the packaging line, Eur. J.
Pharm. Biopharm., 51, 9-16
[55] Morgano, M.A., Faria, C.G., Ferrão, M.F., 2005,Determinaç
ão de proteína em café cru por espectroscopia NIR e regressão
PLS, Ciênc. Tecnol. Aliment., 25, 25-31
[56] Souza, J.S., and Ferrão, M.F., 2006, Aplicações da
espectroscopia no infravermelho no controle de qualidade de
medicamentos contendo diclofenaco de potássio. Parte I:
Dosagem por regressão multivariada, Br. J. Pharm. Sci., 42,
437-445
