American Journal of Analytical Chemistry, 2010, 1, 34-39
doi:10.4236/ajac.2010.11005 Published Online May 2010 (http://www.SciRP.org/journal/ajac)
Validation of HPLC and FIA Spectrophotometric Methods
for the Determination of Lansoprazole in Pharmaceutical
Dosage Forms and Human Plasma
Idrees F. Al-Momani*, Majdoleen H. Rababah
Chemistry Department, Yarmouk University, Irbid, Jordan
Received January 10, 2009; revised February 21, 2009; accepted February 23, 2009
Abstract
A chromatographic and aspectrophotometric methods for the quantitative determination of lansoprazole in
pharmaceutical combinations and human plasma were developed. The analytical parameters were studied
according to International Conference on Harmonization guidelines. The Flow Injection Analysis (FIA)
method is based on the oxidation of lansoprazole by a known excess of N-bromosuccinimide (NBS) in an
acidic medium, followed by a reaction of excess oxidant with chloranilic acid (CAA) to bleach its purple
color. The separation was carried out using RP-C18 column with a mobile phase composed of ACN: TEA:
phosphate buffer (60: 0.2: 39.8 v/v) adjusted to pH = 4.
Keywords: Lansoprazole, FIA, HPLC, Pharmaceutical Products, Human Plasma
1. Introduction
Lansoprazole, 2-[[[3-methyl-4-(2,2,2-trifluoroethoxy)-2-
pyridinyl]methyl]sulfinyl]-1H-benzimidazole, is an im-
portant proton pump inhibitor that suppresses gastric acid
secretion by specific inhibition of the gastric H+, K+
ATPase enzyme system. Lansoprazole is effective in the
treatment of various peptic diseases, including gastric
and duodenal ulcer and reflux esophagitis, Zollinger-
Ellison syndrome [1]. Proton pump inhibitors are unsta-
ble at a low pH, therefore, the oral dosage forms are sup-
plied as enteric-coated granules encapsulated in a gelatin
shell. Owing to the vital importance of the drug, the de-
velopment of sensitive, simple and fast methods for its
determination is of urgent need. [1,2].
A survey of literature has revealed several analytical
methods for the determination of lansoprazole in bio-
logical fluids and in pharmaceutical products. These in-
clude; high-performance liquid chromatography (HPLC)
[3-7], electrochemical [8-10] and spectrophotometric
methods [11-13]. The literature reports few spectropho-
tometric methods for the quantitation of lansoprazole.
The reported methods need heating and long time for the
color formation. According to our knowledge, only one
FIA method was reported in the literature for the deter-
mination of lansoprazole. In addition, some of the re-
ported HPLC methods need sophisticated instruments or
do not describe analytical parameters that are very im-
portant for the validation of analytical procedure such as
accuracy, specificity, robustness, limit of detection (LOD)
and limit of quantitation (LOQ).
Since lansoprazole is acid labile, it is important to de-
velop and validate analytical methods for its determina-
tion in the presence of its degradation products. The
HPLC method has been highly used in the quality control
of drugs because of their sensitivity, reproducibility and
specificity. The FIA spectrophotometric method is very
simple, rapid and economical and allows the determina-
tion of drugs with sufficient reliability. The present work
reports the development and validation of a FIA and
HPLC methods for the estimation of lansoprazole in
pharmaceutical products and in human plasma.
2. Experimental
2.1. Chemicals
All chemical used were in pure grade and used as re-
ceived without further purification. The active ingredient
lansoprazole was supplied by the United Pharmaceuticals.
All pharmaceutical products used in this work were pur-
chased from the local market. Acetonitrile (ACN) and
methanol were HPLC grade and obtained from LAB-
SCAN. Triethylamine (TEA) was obtained from Cam-

I. F. AL-MOMANI ET AL.35
brian Chemicals. Phosphoric acid, N-bromosuccinimid and
Chloranilic acid were obtained from Fluka Chemicals
Ltd. Ultrapure water was used to prepare all solutions.
All solutions were prepared daily.
2.2. Instrumentation and Analytical Conditions
The FIA system was assembled from 0.51 mm micro line
tubes. This manifold consists of three microline tubes
(Figure 1). The first tube contains the carrier (0.2 M HCl)
which carries the sample toward the first reaction coil in
order to react with the reagent (NBS) which is pumped in
the second tube. The CAA stream was then added at a
rate of 1.0 mL/min in a confluence manner down stream
to ensure rapid and adequate mixing. The excess NBS
was then allowed to react with the CAA in the second
reaction coil (RC2). After injection, the valve was re-
turned to the load position when the maximum change in
absorbance value has been reached. The absorbance of
the remaining CAA was monitored at 530 nm by a Var-
ian DMS-100 UV-Visible spectrophotometer equipped
with an 18 µL flow cell.
The HPLC method was performed on a Knauer model-
501 liquid chromatograph system. The system is equipped
with a 20 µL manual injector, 10 mL ceramic head pump
and a programmable variable wavelength UV detector.
Eurochrom software was used for all chromatographic
measurements. A reversed-phase column (15 cm × 4.0
mm ID., 5 µm particle size, C18 column) was used at
ambient temperature. Lansoprazole was eluted isocrati-
cally with a flow rate of 0.5 mL/min and monitored at
285 nm. The mobile phase was prepared by using ACN:
TEA:phosphate buffer (60:0.2:39.8, v/v) adjusted to pH
= 4 using phosphoric acid. The mobile phase was filtered
using 0.45 µm PTFE filters, stirred and degassed before
use.
2.3. Preparation of the Standard Solutions
1) N-bromosuccinimid (NBS): Accurately weighed 44.5
mg of NBS was transferred to 250 mL volumetric flask
and dissolved in 0.1 M HCl. The final concentration was
Sample
RC1
Q; ml/min
Waste
C
R1
R2
X
RC2
Waste
Spectrophotometer
(530 nm)
FC
Computer
P
Sample
RC1
Q; ml/min
Waste
C
R1
R2
X
RC2
Waste
Spectrophotometer
(530 nm)
FC
Computer
P
Figure (1): Schematic diagram of the proposed FIA system.
P, peristaltic pump; X, confluence point; C, carrier solution,
0.2 M HCl; R1, 1.0 mM NBS; R2, 1.0 mM CAA; RC1 and
RC2 are the reaction coils; FC, flow cell.
1.0 mM.
2) Chloranilic acid (CAA): Accurately weighed 52.0
mg of CAA was transferred to 250 mL volumetric flask
and dissolved in ultrapure water. The final concentration
was 1.0 mM.
3) Lansoprazole standard solutions: Accurately weighed
100.0 mg of lansoprazole reference standard was trans-
ferred to 100 mL volumetric flask and dissolved in 0.1 M
HCl. Standard solutions for linearity study were prepared
by diluting the calculated volumes of the stock solution
with 0.1 M HCl.
4) Internal standard: The internal standard (IS) solu-
tion was prepared by dissolving 12.5 g of xanthon in 250
mL of methanol. The final concentration was 50 μg/mL.
The solution was then used as a solvent to prepare all
other solutions to be analyzed by HPLC.
2.4. Preparation of the Sample Solutions
1) Capsules: The contents of 10 capsules were emptied
and finely powdered. The powder amount equivalent to
20.0 mg of lansoprazole was transferred to a 100 mL
volumetric flask, stirred for 10 min with 0.1 M HCl and
then diluted to volume with 0.1 M HCl. The solution was
then filtered through 0.2 µm cellulose acetate syringe
filters. The filtrate was used to prepare different concen-
trations within the linearity range by proper dilution with
0.1 M HCl. Samples to be analyzed by the HPLC were
diluted by the internal standard solution.
2) Spiked plasma samples (for HPLC method only):
Plasma samples were supplied by the Blood Bank (Am-
man) and stored as soon as possible at –4℃. After being
thawed, known amounts of the drug under investigation
were added to drug-free plasma (100-300 µL of the 1000
μg/mL per 0.5 mL plasma). After that, 1 mL of water
was added. The mixture was vigorously mixed in a tube
for 1 min and then allowed to stand for 10 min. This
mixture was applied to a solid phase extraction cartridge
(1 g of C18, obtained from Supelco Company) that had
previously been activated with 1.0 mL of methanol fol-
lowed by 1.0 mL of water. The cartridge was then
washed with 2.0 mL of water and then with 1.0 mL of
40% methanol in water. Lansoprazole was then eluted
with 2.0 mL of methanol. The solvent was then evapo-
rated to dryness under gentle stream of nitrogen and the
residue was re-dissolved in 5 mL of the internal standard
solution and injected onto the HPLC column.
3) Recovery: The recovery following the extraction
procedure was determined by comparing the peak areas
of blank plasma sample extracted according to the above
procedure with those of non-extracted control samples.
The control samples were prepared by mixing solutions
containing the same amounts of the drug (same concen-
trations added to plasma samples) was directly injected
into the HPLC apparatus.

I. F. AL-MOMANI ET AL. 36
3. Results and Discussion
3.1. Development of the Methods
3.1.1. FIA Method
The proposed FIA method allows a rapid and economical
quantitation of lansoprazole in pharmaceutical formula-
tions without any time-consuming sample preparation. It
was found that NBS can oxidize lansoprazole in an
acidic medium. In addition, it reacts immediately with
chloranilic acid (CAA) in an acidic medium to bleach out
its purple color. Therefore, after the oxidation of lanso-
prazole by NBS, the excess NBS was reacted with the
CAA. The absorption spectrum of the remaining CAA
which has a maximum absorption at 530 nm is recorded.
Consequently, the different parameters affecting the
oxidation reaction, and hence the subsequent determina-
tion were optimized.
The effect of the acidity on the completeness of the re-
action, and consequently on the analytical signal, was
studied over acidic and basic pH ranges. Different buffer
solutions (acetate, citrate, borate and phosphate) were used
as carriers. No significant influence for the buffer type on
the analytical signal was observed. However, all results
indicated that the reaction was better carried out in an
acidic medium. Therefore, the reactions were carried out
using different types of acids with different concentrations
as carriers. Hydrochloric acid gave the best results, and
therefore, was used for further investigations. Gradual
increase in the analytical signal was observed upon in-
creasing the HCl concentration. However, the stability of
the baseline and consequently the reproducibility of the
results were significantly reduced at higher HCl concen-
trations. Therefore, 0.2 M HCl was used as a carrier as it
gives reasonable sensitivity and baseline stability.
The influence of changing CAA concentration on the
analytical signal was studied at different concentrations
of NBS (0.2-1.5 mM). Fixed volumes (100 μL) of lanso-
prazole were injected into the HCl stream (Figure 1).
Maximum analytical signals were obtained when the
concentration of CAA was 1.0 mM. In addition, dif-
ferent concentrations of NBS were tested. However, for
all NBS and CAA combinations tested, best results were
obtained when the NBS-to-CAA ratio was 1:1. Further-
more, maximum analytical signal was obtained when 1.0
mM NBS was used. Concentrations that are higher than
1.0 mM for NBS were not tested due to its low solubility.
Therefore, 1.0 mM NBS was used throughout this work.
The effect of the reagents flow rate was studied keep-
ing other conditions constant, over the range 1.0-4.8
mL/min, with equal flow in the three channels. The high-
est signals were obtained when the total flow rate was 3.0
mL/min. At higher flow rates, irreproducible results and
considerable decrease in the analytical signal was ob-
served. A flow-rate of 1.0 mL/ min for each channel was
chosen as a compromise between the peak shape, the sen-
sitivity and the sampling time. With a flow rate of 1.0
mL/min, the analysis time for one injection was less than
50 seconds and the sample throughput was over 70 sam-
ples/h.
Two reaction coils were used in the manifold, as
shown in Figure 1. The first coil (RC1), in which the
oxidation of the drug by NBS took place, was changed
over the range 30 to 150 cm. A considerable increase in
the analytical signal was observed upon increasing the
coil length up to 120 cm, and started to decrease after
that. This indicates that the reaction between the drug
under investigation and NBS was fast, and a further in-
crease in the reaction coil length resulted in a significant
peak broadening and a longer time to go back to the
baseline. Therefore, the length of the first reaction coil
(RC1) was chosen to be 120 cm to ensure high sensitiv-
ity and a high measurement rate. Similarly, a significant
change in the analytical signal was observed when the
second reaction coil (RC2) was increased from 30 to 150
cm. Maximum analytical signals were obtained when
RC2 was 50 cm.
In order to investigate the influence of the injected
sample volume on the analytical signal, different lengths
of the sample loop were installed on the injector and
tested. As expected, an increase in the injected sample
volume leads to an increase in the peak height. Conse-
quently, the sensitivity of measurements could be im-
proved by increasing the sample volume. However, in-
creasing the sample volume lead to an increase in the
peak width and time for the signal to retain to the base-
line. Thus, a 100 L volume was chosen that produced a
reasonable sensitivity and sampling rate.
3.1.2. HPLC Method
Chromatographic separation of lansoprazole from its
degradation products was carried out using Novapak C18
column. The chromatographic conditions were adjusted
in order to provide a good performance of the assay.
Several mobile phases were prepared and tested in order
to achieve these requirements. Mobile phase selection
was based on peak parameters (symmetry, tailing), run
time, easy of preparation and cost. In these trials the
separation time was long (> 10 min) with a considerable
tailing in lansoprazole peak. Therefore, in order to mini-
mize the analysis time and to improve the separation
efficiency, triethylamine (TEA) was added to the mobile
phase in different ratios. Figure 2 shows a typical chro-
matogram obtained from the analysis of a standard and a
sample solution of lansoprazole using the proposed
method. As shown, the lansoprazole peak is symmetrical
and free from any chemical interference.
3.2. Validation of the Proposed Methods
The methods were validated according to International
Conference on Harmonization guidelines [14] for valida-

I. F. AL-MOMANI ET AL.37
0.2
0.4
0.6
0510 15
0.0
Abs.
Time (min)
0.2
0.4
0.6
0510 15
0.0
Abs.
Time (min)
0.2
0.4
0.6
0510 15
0.0
Abs.
Time (min)
(A) (B) (C)
IS
Lansoprazole
0.2
0.4
0.6
0510 15
0.0
Abs.
Time (min)
0.2
0.4
0.6
0510 150510 150510 15
0.0
Abs.
Time (min)
0.2
0.4
0.6
0510 15
0.0
Abs.
Time (min)
0.2
0.4
0.6
0510 150510 150510 15
0.0
Abs.
Time (min)
0.2
0.4
0.6
0510 15
0.0
Abs.
Time (min)
0.2
0.4
0.6
0510 150510 150510 15
0.0
Abs.
Time (min)
(A) (B) (C)
IS
Lansoprazole
(a) (b) (c)
Figure 2. (a) Chromatograms for pure lansoprazole; (b) one
of the commercial product, Lansozole; (c) plasma extract
Concentration of lansoprazole in samples was 75 μg/mL.
tion of analytical procedures. Analysis of variance (ANO-
VA) was used to verify the validity of the methods.
3.2.1. FIA Method
The calibration curve for the determination of lansopra-
zole was obtained under the optimum conditions. The
calibration graph was constructed by plotting concentra-
tion versus peak area and showed good linearity in the 5-
150 μg/mL range. The representative linear equation was
Y = 8.62 × 10-4 X + 1.70 × 10-3, with a correlation coef-
ficient (r = 0.9988) highly significant for the method.
The limit of detection (LOD) and limits of quantitation
(LOQ) were determined on the basis of response and
slope of the regression equation. The LOD and LOQ
were found to be 5.0 and 16.4 μg/mL, respectively indi-
cating a high sensitivity of the method.
The intra-day (within-day) precision was evaluated by
replicate analysis of lansoprazole within the linearity
range at different time intervals. Three measurements
were taken within the same day. Each time, a new cali-
bration graph was constructed. The result obtained shows
RSD of 1.7% indicating good intra-day precision. Simi-
larly, the inter-day (different days) precision was evalu-
ated on different days (3 days). The results indicated
high precision, as the percent RSD was 2.3%. Figure 3
shows the flow signals for the calibration graph and re-
producibility test. The reproducibility of the peak height
was very good and the relative standard deviation of 10
injections was 1.4% (Figure 3(b)).
The accuracy of the proposed FIA method was deter-
mined by analyzing lansoprazole in synthetic mixtures.
Percentage recovery from synthetic mixtures was deter-
mined by comparing the peak areas obtained from com-
mon excipients spiked with known amounts of lansopra-
zole. Synthetic mixtures containing different concentra-
tions of lansoprazole, in the presence of more than 100
folds of common additives were prepared. The additives
that have been used in this study are; sodium saccharide,
and citric acid. The undissolved material was filtered off
10
30
50
70
90
110
0 3 6 91215
Time, (min)
Peak Height
Blank
5 ppm
10 ppm
25 ppm
50 ppm
80 ppm
Time
(B)
(A)
10
30
50
70
90
110
0 3 6 91215
Time, (min)
Peak Height
Blank
5 ppm
10 ppm
25 ppm
50 ppm
80 ppm
10
30
50
70
90
110
0 3 6 91215
Time, (min)
Peak Height
Blank
5 ppm
10 ppm
25 ppm
50 ppm
80 ppm
Time
(B)
(A)
(a) (b)
Figure 3. Flow signals for the calibration graph and repro-
ducibility test of lansoprazole.
Table 1. Recovery of lansoprazole from synthetic mixtures
and human plasma samples.
Sample Added
(μg/mL) % Recovery ± SD (n = 5)
FIA HPLC
Synthetic 40 102.3 ± 1.3 101.2 ± 0.9
80 97.8 ± 0.7 99.7 ± 0.6
120 98.6 ± 0.8 97.4 ± 2.4
Plasma 20 95.51 ± 3.2
50 96.9± 2.0
100 97.3 ± 1.1
before injection. The results obtained were compared
with expected values and presented in Table 1. No sig-
nificant changes were observed in the results and recov-
eries close to 100% were achieved at all concentrations
and the RSD does not exceed 2.5%. The closeness of the
results to the label claim supports the accuracy of the
method.
3.2.2. HPLC Method
The calibration curves for lansoprazole were constructed
by plotting concentration versus peak area and showed
good linearity in the 2.0-120 μg/mL range. The repre-
sentative linear equation was Y = 4.90 × 10-3 X + 1.10 ×
10-3, with a correlation coefficient (0.9993) highly sig-
nificant for the method. Figure 2 shows HPLC chroma-
tograms for 75 μg/mL of (a) lansoprazole standard, (b)
commercial product, lansazole, (c) plasma extract. As
shown, excipients used as additives in pharmaceutical
formulations did not interfere in the proposed proce-
dures.
The LOD and LOQ were found to be 2.0 and 7.0 μg/mL,
respectively indicating a high sensitivity of the method.
The precision of the method was determined by repeat-
ability (intra-day) and (inter-day) and was expressed as
%RSD of a series of measurement. The result obtained

I. F. AL-MOMANI ET AL. 38
shows RSD of 0.83% indicating good intra-day precision.
Inter-day variability was calculated from assays on 3
days and shows a mean RSD of 1.85%.
The accuracy of the HPLC method was determined by
analyzing lansoprazole in synthetic mixtures. Same pro-
cedure describe for the FIA was followed. However, all
samples in this case were diluted by the internal standard
solution. The average recovery was close to 100%, indi-
cating an agreement between the true value and the value
found (Table 1).
The specificity was determined for the HPLC method.
Sample solutions of lansoprazole were submitted to ac-
celerated degradation by heat (70℃ for 1.0 h), addition
of 1.0 M HCl, and oxidation by NBS, in order to verify
that none of the degradation products of the analyte in-
terfered with the quantitation of drug. The described
HPLC method is specific. No interfering peaks were ob-
served in degraded solutions and the degradation prod-
ucts were well resolved from the parent lansoprazole
peak (Figure 4).
The robustness of the HPLC method was determined
by analysis of samples under a variety of conditions such
as small changes in the pH (3.7-4.3) and in the percent-
age of acetonitrile (55-65%) in mobile phase and chang-
ing the column. The effect on retention time and peak
parameters were studied. The method was found to be
robust when the column and the mobile phase were var-
ied. During these investigations, the retention times were
modified, however the area and symmetry of peaks were
conserved.
3.3. Applicability of the Proposed Methods
3.3.1. FIA Method
In order to evaluate the applicability of the proposed FIA
method to routine pharmaceutical analysis, commercial
pharmaceutical products containing lansoprazole were
analyzed. Results obtained are summarized in Table 2.
As shown, the recoveries are excellent and were above
95%. The closeness of the results to the label claim sup-
ports the accuracy of the method.
The applicability of the proposed FIA method for
plasma samples was also investigated. Plasma samples
Time (min)
(A) (B)
0.2
0.4
0.0
Abs.
051015 20
Lansoprazole
0.2
0.4
0.0
Abs.
0510 15 20
Lansoprazole
Time (min)Time (min)
(A) (B)
0.2
0.4
0.0
Abs.
051015 20051015 20
Lansoprazole
0.2
0.4
0.0
Abs.
0510 15 200510 15 20
Lansoprazole
Time (min)
(a) (b)
Figure 4. Chromatograms of (a) acid degraded lansoprazole
and (b) NBS oxidized lansoprazole.
Table 2. FIA and HPLC results for the analysis of lanso-
prazole in pharmaceutical preparations.
%Recovery ± RSD (n = 6)
Trade Name &
Labeled Claim
Taken
(μg/mL) FIA HPLC
40.0 101.7  4.8 101.2  0.2
80.0 99.3  0.3 100.5  1.9
(Lansazol)
(15mg/Cap)
120 97.8  0.6 100.5  0.9
40.0 101.3  1.8 102.2 ± 2.4
80.0 100.2  3.3 101.7 ± 1.7
(Lansomid)
(15mg/Cap)
120.0 96.5  1.7 100.7  1.9
were spiked by different concentrations of lansoprazole.
All samples were cleaned up by solid phase extraction in
a similar manner to that followed before. Injection of
these samples gave higher absorbance readings than the
corresponding standards containing same amounts of
lansoprazole. This means that the plasma components
have interfered with the analysis. Precisely, most of the
NBS have been consumed by the plasma components.
These finding indicate that the proposed FIA method is
not applicable for the determination of lansoprazole in
human plasma.
3.3.2. HPLC Method
To evaluate the general applicability of the HPLC method,
lansoprazole was analyzed in different sample matrices.
The accuracy of this method was validated by the analy-
sis of these drugs in commercial pharmaceutical formu-
lations and spiked plasma samples. Results are summa-
rized in Tables 1 and 2. For the pharmaceutical products,
the recoveries were satisfactory and close to 100%. The
closeness of the results obtained to the label claimed
supports the accuracy of the method. No interferences
were observed from any additives in any of the products
analyzed.
The proposed HPLC procedure was further validated
using spiked human plasma samples. In all cases, no in-
terferences from the indigenous plasma components
were observed (Figure 2(c)). The recoveries were in the
range 95-97%. The simplicity of the proposed extraction
procedure and the high extraction efficiency are among
the essential features of the proposed HPLC method,
making this method suitable for routine, efficient and fast
extraction of lansoprazole from complex matrices.
3.3.3. Comparison of the FIA Results with the HPLC
Results
The proposed analytical methods were compared using
statistical analysis. The student’s t-test was applied and
does not reveal significant difference between the ex-
perimental values obtained in the sample analysis by the

I. F. AL-MOMANI ET AL. 39
two methods. The calculated t-value (1.18) was found to
be less than the tabulated t-value (2.2) at 5% significance
level.
3.4. Conclusions
The determination of lansoprazole in pharmaceutical
products can be performed by flow injection spectro-
photometric analysis with a relative standard deviation of
< 5% and a rate of at least 70 samples per hour. The de-
veloped FIA method is accurate, precise, simple, and
economic in consumption of samples and reagents, re-
producible and can be applied for the determination of
these drugs in different pharmaceutical products.
The HPLC assay of lansoprazole has been shown to be
of general applicability to commercially available prod-
ucts and spiked human plasma samples. It could be used
for the assay determination in the range of 2.0-120 μg/mL
with a relative standard deviation of < 3%. The method is
accurate, precise and specific. The described HPLC as-
say can be easily applied for the quantification of the
degradation products.
4. Acknowledgements
The financial support from Yarmouk University is
gratefully acknowledged. The authors would like to
thank Al-Hikma pharmaceuticals, Amman-Jordan, for
providing the standard and the excipients.
5
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