Current Pharmaceutical Analysis, 2008, 4, 231-237 231
1573-4129/08 $55.00+.00 © 2008 Bentham Science Publishers Ltd.
Development and Validation of a Rapid Chemometrics-Assisted Spectro-
photometry and Liquid Chromatography Methods for the Simultaneous
Determination of the Phenylalanine, Tryptophan and Tyrosine in the
Pharmaceutical Products
Siavash Riahi
a,b,
*, Mohammad R. Ganjali
b
, Eslam Pourbasheer
b
, Faten Divsar
c
, Parviz Norouzi
b
and
Marzieh Chaloosi
c
a
Institute of Petroleum Engineering, Faculty of Engineering, University of Tehran, P. O. Box 11365-4563, Tehran, Iran
b
Center of Excellence in Electrochemistry, Faculty of Chemistry, University of Tehran, P. O. Box 14155-6455, Tehran,
Iran
c
Factually of Chemistry, University of Tarbiat Moalem, Tehran, Iran
Abstract: The simultaneous multicomponent analysis is usually carried out using multivariate calibration models, such as
the partial least squares (PLS). The genetic algorithm (GA) is a suitable method for the wavelength selection for the PLS
calibration of the mixtures with almost identical spectra and without loss of the predictive ability, using the spectropho-
tometric method. In this work, a simple and precise method for rapid and accurate simultaneous determination of phenyla-
lanine, tryptophan and tyrosine is proposed with the employment of the PLS regression together with GA for the variable
selection. The method was successfully applied to the quantitation of these amino acids in aminoplasmal serum, providing
results in agreement with those obtained by high performance liquid chromatography (HPLC).
Keywords: Spectrophotometric, Amino acids, Chemometrics, Genetic Algorithm, Aminoplasmal serum.
1. INTRODUCTION
The identification and determination of amino acids are
important in studying human diseases and are routinely per-
formed especially in clinical and biomedical laboratories [1,
2]. Many types of samples, such as biological fluids, serum
albumin, food and protein hydrolysates, contain these amino
acids. Within the nutrition field, essential amino acids play
an important role and are considered as industrially interest-
ing metabolites [3].
Tryptophan (Try) interposes in brain functioning [4],
phenylalanine (Phe) is the diagnostic marker for phenylke-
tonuria (PKU) and tyrosine (Tyr) for tyrosinemia in the
screening of IEM (Inborn Errors Metabolism) [5-7]. It has
also been reported that patients with schizophrenia have al-
tered brain levels of the essential amino acid, tyrosine, the
precursor for the synthesis of dopamine [8].
Commercially available amino acid analyzers are often
used for the determination of amino acids. In the recent
years, a number of clinical institutes that have introduced
HPLC methods for the IEM screening have increased. Sev-
eral specific instruments for the analysis of amino acids are
based on liquid chromatography [9], HPLC [10], thin layer
chromatography, GC-MS spectrometry analysis [11] and
capillary electrophoresis [12-14]. It should be mentioned that
although chromatographic techniques provide accurate re-
*Address correspondence to this author at the Institute of Petroleum Engi-
neering, Faculty of Engineering, University of Tehran, Iran; Tel: +98-21-
88333058; Fax: +98-21-88632975; E-mail: riahisv@khayam.ut.ac.ir
sults, they may be unsuitable for the analysis of large sets of
samples, because the separation step is time-consuming.
Nowadays, simpler and faster procedures are needed to sat-
isfy the great demand of amino acid determinations in fields
such as food processing, biochemistry, pharmaceuticals and
clinical analysis.
Phe, Try and Tyr show typical absorbance bands in the
ultraviolet region, between 190 and 235 nm. The simultane-
ous spectrophotometric determination of these amino acids
shows that some difficulties occur, due to the high overlap-
ping between their spectra. Multivariate calibration methods
are being applied successfully to the multicomponent deter-
mination to overcome some of the drawbacks of the classical
methods.
The application of quantitative chemometrics methods,
particularly partial least squares (PLS), to multivariate
chemical data is becoming more widespread, owing to the
availability of the digitized spectroscopic data and commer-
cial software for laboratory computers [13-15]. The advan-
tage of multicomponent analysis along with partial least
squares in mixtures is the demonstration of fast separation
steps. The theory and application of partial least squares
(PLS) in spectrometry have previously been discussed by
several workers [16, 17].
Genetic algorithm (GA) is a very useful technique in the
variable selection problems, because the relationship be-
tween the presence/absence of the variables in a calibration
model and the prediction ability of the model, specifically
for the PLS models, is very complex and the mathematical