Pharmacology & Pharmacy, 2013, 4, 511-519
http://dx.doi.org/10.4236/pp.2013.47074 Published Online October 2013 (http://www.scirp.org/journal/pp)
511
The Quality of Medicines in Community Pharmacies in
Riyadh, Saudi Arabia: A Lot Quality Assurance Sampling
(LQAS)-Based Survey
Hani M. J. Khojah1,2*, Henrik Pallos3, Naoko Yoshida1, Manabu Akazawa4, Hirohito Tsuboi1,
Kazuko Kimura1
1Department of Drug Management and Policy, Graduate School of Natural Science and Technology, Kanazawa University, Kana-
zawa, Japan; 2Department of Clinical and Hospital Pharmacy, College of Pharmacy, Taibah University, Madinah, KSA; 3Department
of International Pharmaceutical Sciences, Graduate School of Natural Science and Technology, Kanazawa University, Kanazawa,
Japan; 4Department of Public Health and Epidemiology, Meiji Pharmaceutical University, Kiyose, Japan.
Received August 5th, 2013; revised September 5th, 2013; accepted September 21st, 2013
Copyright © 2013 Hani M. J. Khojah et al. This is an open access article distributed under the Creative Commons Attribution Li-
cense, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
ABSTRACT
Objectives: To classify community pharmacies (CPs) in Riyadh, Saudi Arabia, in terms of the quality of medicines sold
by them, using the lot quality assurance sampling (LQAS) technique with a predefined threshold. Methods: Riyadh
CPs were divided into 2 categories (“lots” for the purpose of LQAS), i.e., chain and independent CPs. Upper and lower
rate thresholds for CPs that sell low-quality medicines were predefined as 20% and 5%, respectively. Consumer and
provider risks were predefined as 0.05 and 0.10, respectively. The calculated number of randomly selected CPs required
in each lot was 36; then, sale of low-quality medicines in >3 CPs implies a prevalence of >20% of such CPs according
to LQAS. A randomly selected brand of amoxicillin (selected as a quality indicator of medicines because it is both
widely counterfeited and heat-sensitive) was purchased from each pharmacy by a “mystery shopper”, checked for au-
thenticity, and analyzed for drug content and content uniformity using a validated HPLC method. Results: Substandard
amoxicillin was purchased in 9 pharmacies (4 chains and 5 independent). Both lots were thus rejected as unacceptable,
which may indicate that consumers in Riyadh are at risk of purchasing substandard medicines at CPs. Conclusions: The
quality of medicines sold in CPs in Riyadh did not meet our acceptability criterion, and appropriate intervention by de-
cision makers is recommended. LQAS proved to be a practical, economical, and statistically valid sampling method for
surveying the quality of medicines. It should enable decision makers to allocate resources for improvement more effi-
ciently.
Keywords: Amoxicillin; Antibiotic; Quality of Medicines; Lot Quality Assurance Sampling; Saudi Arabia; Community
Pharmacy
1. Introduction
Low-quality medicines are a global issue because of their
increasing prevalence and the potentially serious conse-
quences of their use [1,2]. Although developing countries
are the principal targets of counterfeiters, developed
countries also face many of the same risks [3,4]. Es-
sential medicines (e.g., antimicrobials) are the most
frequently targeted products in developing countries [5-
8].
Low-quality medicines may be either counterfeit or
substandard [9,10]. Regardless of the product quality and
amount of active ingredients, counterfeit medicines are
defined as those made by unauthorized manufacturers
with the intention of cheating, and this definition covers
both the medicine and its packaging. Substandard me-
dicines are produced by legitimate manufacturers, but do
not fulfill the manufacturing quality standards or do not
contain the correct amount of active ingredient(s). In
addition, medicines that have passed their expiration date
or that have deteriorated due to improper distribution
and/or storage conditions (i.e., degraded medicines) may
also be considered substandard, even if they were ori-
ginally genuine and of good quality [11].
Studies with sound and replicable methodology on the
*Corresponding author.

The Quality of Medicines in Community Pharmacies in Riyadh, Saudi
Arabia: A Lot Quality Assurance Sampling (LQAS)-Based Survey
512
quality of medicines in developing countries are very
limited. Convenience sampling is widely used for this
purpose, even though bias is clearly introduced because
usually only accessible pharmacies or outlets are selected.
Formal random sampling generally requires a larger
sample, longer surveying time, and more resources. For
these reasons, Lot Quality Assurance Sampling (LQAS)
has been proposed as an economical technique to survey
the quality of medicines sold in community pharmacies
(CPs) [11]. LQAS was developed in the 1920s to assess
the quality of industrial products by inspecting random
samples [12]. It was later adapted for a variety of health
surveys and settings, though not surveys of the quality of
medicines in the supply chain [13,14]. Because LQAS
uses a relatively small sample, it cannot determine the
prevalence (rate) of outlets that sell low-quality medi-
cines, but rather provides a way to classify the rate as
either acceptable or unacceptable in terms of predeter-
mined criteria. Thus, it may be helpful to enable decision
makers to properly allocate and distribute resources
among various supervisory areas, and also provides an
indication as to whether or not larger-scale, randomized
surveys are required.
In Saudi Arabia self-medication is common and var-
ious prescription medicines, including antibiotics, can be
purchased from CPs without a prescription, despite the
government’s regulations [15,16]. Recently, the Saudi
Food and Drug Authority (SFDA) was es- tablished as an
independent corporate body that reports directly to the
President of the Council of Ministers. It is responsible for
ensuring the safety of food and drugs for human and
veterinary use and the safety of biological and chemical
substances and medical devices [17].
Among antibiotics, amoxicillin is widely used in de-
veloping countries, and it is included in the list of es-
sential drugs issued by the World Health Organization
(WHO) [18]. It is also considered an essential drug in
primary health care in Saudi Arabia [19]. It is also among
the most widely counterfeited medicines in developing
countries [3,5]. Substandard amoxicillin has already been
identified in Saudi Arabia in one study [8]. Furthermore,
amoxicillin products, including suspensions and capsules,
are sensitive to heat and may degrade easily at tem-
peratures above 30˚C [20]. Therefore, we focused on
amoxicillin as an indicator of the quality of medicines in
the supply chain in Saudi Arabia, where high tempera-
tures are common.
We aimed to explore the quality of amoxicillin cap-
sules and tablets sold in CPs in Riyadh, Saudi Arabia, as
an indicator of the quality of medicines sold in these
pharmacies, using the LQAS technique. Based on a
review of the literature on the quality of amoxicillin in
developing countries [3,5,8,21,22], we formulated as our
null hypothesis that more than 20% of the CPs in Riyadh,
in either the chain or independent category, sell low-
quality amoxicillin.
2. Methods
This study was approved by the Ethical Committee of
Kanazawa University and by the SFDA. Samples in the
original packaging were collected between September 21
and October 3, 2010, individually placed in sealed bags,
packed in thermally insulated plastic cool boxes, and
shipped to Kanazawa University, Japan, via a secure
courier after obtaining the necessary clearance docu-
ments. The analysis was performed in the Department of
Drug Management and Policy at Kanazawa University
between May 25, 2011 and February 7, 2012 (before the
expiration dates of all samples). The cool boxes were
kept in the laboratory at a controlled room temperature of
22˚C until analysis.
Because 2 levels of sampling (pharmacies and amo-
xicillin brands) were included in this study, the term
“sample” is used to indicate amoxicillin samples and the
term “subject” for the pharmacies selected for the study.
The term “target pharmacy” refers to a pharmacy that sold
low-quality amoxicillin. In general, the survey methodo-
logy and reporting were consistent with the Medicine
Quality Assessment Reporting Guidelines (MEDQUARG)
proposed by Newton et al. [11].
2.1. Selection of Pharmacies
A list of registered CPs in Riyadh was obtained from the
Saudi Ministry of Health (MOH) in July 2010 (1367
pharmacies). The pharmacies were divided into 2
categories, i.e., chain and independent (869 and 498
pharmacies, respectively). An independent pharmacy was
defined as one belonging to a group of ≤3 pharmacies,
whereas a chain pharmacy was defined as one belonging
to a group of >3 pharmacies [23]. Each category was
designated as a “lot”for the purpose of LQAS.
The required number of pharmacies in each lot and the
decision rule were calculated according to the LQAS
technique. The binomial LQAS formula (Figure 1(a)) is
preferred if the population size is either unknown or very
large [24]. In the present study, we used the hypergeo-
metric LQAS model (Figure 1(b)) because each subject
pharmacy was included only once and because the
population size of pharmacies in each lot was known and
relatively small [25,26]. These characteristics allow the
actual errors to be calculated more accurately. In this
model, the gamma function was used for the calculation
of factorials of fractions (Figure 1(c)). A calculator that
uses this calculation method is available online [27].
Studies from developing countries have reported a

The Quality of Medicines in Community Pharmacies in Riyadh, Saudi
Arabia: A Lot Quality Assurance Sampling (LQAS)-Based Survey
513
variety of rates of sale of counterfeit and substandard
antimicrobials ranging from 2.8% to > 50%, with the
majority of the rates lying within the range of 30% - 40%
[3]. In addition, various levels of amoxicillin content,
ranging from 0% to 85% of the labeled amount, have
been reported [3,5,8,21,22]. Based on the above reports,
we adopted the following upper and lower prevalence
thresholds in this study: a lot with a rate of target
pharmacies >20% was classified as a high-prevalence lot
(so that the null hypothesis was not rejected for this lot),
whereas a lot with a rate of target pharmacies ≤5% was
classified as a low-prevalence lot. This criterion for the
low-prevalence lot is considered acceptable, because it is
preferable to devote limited resources to improve CPs in
the high-prevalence lot. The consumer risk (alpha error
based on the null hypothesis) and the provider risk (beta
error) were predetermined to be ≤0.05 and ≤0.10, res-
pectively.
target pharmacies in either lot exceeds the decision value,
the lot is classified as a high-prevalence lot and the null
hypothesis is not rejected. Otherwise, the lot will be
classified as a low-prevalence lot. The LQAS decision
rule only classifies the rate as either >the predefined
upper threshold or ≤the predefined lower threshold. It is
not sensitive to rates between these thresholds. It is worth
mentioning that formal random sampling would have
(a) (b) (c)
The minimum number of subject pharmacies that
produced the lowest combination of cumulative errors at
both thresholds was 36 pharmacies in each lot, with 3 as
the value for the decision rule (Table 1). If the number of
Figure 1. The LQAS Equations. (a) The binomial formula;
(b) the hypergeometric formula; (c) the factorial of a frac-
tion.
Table 1. Part of the calculation process for deciding the required number of subject pharmacies and the dec ision rule .
x Sensitivity
(at upper threshold of 0.20)
Cumulative alpha error
(consumer risk)
Cumulative specificity
(at lower threshold of 0.05)
Beta error
(provider risk) Total error
For chain pharmacies (N = 869) when n = 36
0 0.9997 0.0003 0.1517 0.8483 0.8486
1 0.9972 0.0028 0.4519 0.5481 0.5509
2 0.9855 0.0145 0.7336 0.2664 0.2809
3 0.9512 0.0488 0.9006 0.0994 0.1482
4 0.8783 0.1217 0.9708 0.0292 0.1509
5 0.7591 0.2409 0.9931 0.0069 0.2478
6 0.6027 0.3973 0.9987 0.0013 0.3986
For independent pharmacies (N = 498) when n = 36
0 0.9998 0.0002 0.1471 0.8529 0.8531
1 0.9975 0.0025 0.4481 0.5519 0.5544
2 0.9866 0.0134 0.7348 0.2652 0.2786
3 0.9538 0.0462 0.9039 0.0961 0.1423
4 0.8823 0.1177 0.9732 0.0268 0.1445
5 0.7633 0.2367 0.9941 0.0059 0.2426
6 0.6054 0.3946 0.999 0.001 0.3956
The first 7 rows of probability combinations are shown. x = decision rule, N = population size, n = required number of subject pharmacies, sensitivity = 1 −
cumulative alpha error, Beta error = 1 − cumulative specificity. Minimum accepted errors (and their sum) occur when x = 3 in the round of n when n = 36 for
each lot (shaded areas of the table). This indicates that the smallest required number of subject pharmacies is 36. If the calculation continues, other good com-
binations will be obtained. However, this would require additional pharmacies. At n = 36, the finding of ≤3 target pharmacies indicates that their rate in the
corresponding lot is ≤5%. However, this rate is acceptable according to the predefined thresholds in this study. The finding of >3 target pharmacies means that
eir rate is >20%. Because this rate is unacceptable, the corresponding lot (i.e., category of pharmacy) is rejected. th

The Quality of Medicines in Community Pharmacies in Riyadh, Saudi
Arabia: A Lot Quality Assurance Sampling (LQAS)-Based Survey
514
required a 4- to 5-fold larger number of pharmacies in
each category, and therefore the resources required
would have been 4- to 5-fold greater. This represents a
significant advantage for LQAS.
A list of pharmacies in each category was created and
each pharmacy was coded. The lists were scrambled, and
45 pharmacies (36 + 9) were randomly selected from
each list with MS Excel 2010 (Microsoft Co., USA). The
additional 9 pharmacies represented a reserve for an
estimated dropout rate of 25%. Dropout could be for any
of the following reasons: a) the pharmacy was closed on
the second visit; b) the pharmacy was out of business; c)
the pharmacy did not have the required quantity of
amoxicillin dosage units; or d) the pharmacy refused to
sell amoxicillin without a prescription.
In theory, LQAS sampling can be terminated if the
decision rule is exceeded at an early stage of the survey,
thereby minimizing cost and time requirements, though
this was not the case in the present study.
2.2. Amoxicillin Sampling
The “mystery shopper” technique with the same scenario
was used in purchasing samples [28,29]. The sampler
asked the seller to show him all brands of amoxicillin
capsules and tablets available in 4 - 5 packs (80 dosage
units) because one of the sampler’s friends wanted the
medicine. The sampler also told the seller that he would
call his friend to tell him about the available brands and
strengths to allow the friend to select the product to be
purchased. The brands were numbered in a list reflecting
the order in which the seller presented them, excluding
any clavulanate-containing products. Each strength of a
given brand was treated as a separate brand. A mobile
telephone was used to rapidly generate a random number
between 1 and the highest number on the list with Excel
Mobile. This procedure was conducted while the sampler
appeared to be making the call. In this way, one brand
was randomly purchased from each randomly selected
pharmacy. If the packs were from more than one batch of
the same brand, they were considered as different sam-
ples purchased from the same pharmacy. Packs from the
same batch of the same brand purchased from different
pharmacies were also considered as different samples.
After sampling, the sampling form was immediately
completed outside the pharmacy (Table 2). Samples
were immediately placed in a plastic cool box and the car
air-conditioner was operating effectively during all sam-
pling trips. Amoxicillin brands were coded with the
letters A-P.
2.3. Authenticity Investigations
Dosage units, strips, boxes, and package inserts of all
samples were visually inspected. Parts of all those items
Table 2. Sampling information.
Pharmacy code and type Dosage form
Sample code Strength
Sampling date Package size
Package condition and type Registration number in
Saudi Arabia
Trade name Batch number
Manufacturer’s name Manufacture date
Manufacturer’s country Expiration date
Distributor in Saudi Arabia Price
were sent to the corresponding manufacturers for authen-
ticity confirmation. The SFDA was contacted to verify
the registration status of the products.
2.4. Analysis and Materials
The samples were analyzed in the order of their expira-
tion dates. The content uniformity test was performed
according to the 34th edition of the United States
Pharmacopeia (USP), but using a shorter HPLC column
(15 cm instead of 25 cm) [30,31]. The use of the shorter
column would not have affected the results, since the
method was validated. For every sample the amoxicillin
content, which should range from 90.0% - 120.0% for
capsules and 90.0% - 110.0% for tablets, according to the
USP, was calculated by averaging the content of the
dosage units analyzed in the content uniformity test.
All chemicals used were of analytical grade. Acetoni-
trile, potassium dihydrogen phosphate, and potassium
hydroxide were purchased from Nakalai Tesque (Kyoto,
Japan). Standard amoxicillin, conforming to the USP
Reference Standard (USPRS), was obtained from the
Department of Medical Sciences, Bureau of Drugs and
Narcotics, Ministry of Public Health, Thailand. Standard
cefadroxil, from Sigma (St Louis, MO, USA), was used
as the internal standard.
The HPLC system consisted of the following com-
ponents from JASCO (Tokyo, Japan): a pump (PU-2080
Plus), a UV detector (UV-2075 Plus) set at 230 nm, a
column thermostat (CO-1560), a degasser (DG-980-50),
a system controller (LC-Net II/ADC), and an auto-
sampler (AS-950). The system was equipped with a 4.6 ×
150 mm Shim-pack CLC-ODS (M) column from Shi-
madzu (Kyoto, Japan), filled with 70% methanol. The
system was linked with a computer running ChromNav
software from JASCO (Tokyo, Japan) to analyze the
results and to plot curves and peaks.
A calibration curve was produced daily, using 3
concentrations of standard amoxicillin (0.05, 0.10, and

The Quality of Medicines in Community Pharmacies in Riyadh, Saudi
Arabia: A Lot Quality Assurance Sampling (LQAS)-Based Survey
515
0.2 mg/mL) prepared from a fresh stock solution of 1
mg/mL amoxicillin (on anhydrous base). The linearity of
the standard amoxicillin/diluent solution was maintained
between 0.025 and 0.5 mg/mL and the analytical range
was 0.05 - 0.4 mg/mL. A stock solution of standard ce-
fadroxil (0.2 mg/mL, on anhydrous base) was also fre-
shly prepared daily and was added to all sample and
calibration solutions to obtain a final concentration of 0.1
mg/mL in each solution.
The final sample and calibration solutions were fil-
tered through 0.2 µm Minisart RC 4 syringe filters from
Sartorius Stedim (Dublin, Ireland). All solutions were
used within 6 hours of preparation and analyzed in
triplicate.
For method validation, intra- and inter-day precision
tests were performed using standard amoxicillin, and the
accuracy was evaluated by applying the standard-
addition (spiking) recovery technique, using aliquots of
pre-analyzed samples. All values of standard deviation,
relative standard deviation, and relative error for both
precision and accuracy were <2%, based on a 95%
confidence interval. These values were considered satis-
factory.
3. Results
Eighty-three samples were collected from the 72 phar-
macies. Of these samples, 41 were collected from chain
pharmacies and 42 from independent pharmacies (Table
3). Six samples (7%) were tablets and the others were
capsules. Twenty-eight samples (35%) were locally ma-
nufactured, 47 (57%) were imported from other Arab
countries, and 7 (8%) were imported from Europe. The
samples included 16 brands produced by 10 manu-
facturers. These samples represented all the manufac-
turers registered by the SFDA at the time of sampling.
The dropout rate was 7 and 6 for chain and independent
pharmacies, respectively. Dropouts occurred for the
reasons mentioned above, and no major differences in
reasons for dropping out were found between the in-
dependent and chain categories.
The authenticity of the samples was confirmed by all
manufacturers, and the registration status of each product
and manufacturer was confirmed by the SFDA.
A total of 9 samples (11%), all of which were capsules,
failed the content uniformity test. The failed samples
were purchased from 9 pharmacies (4 chain and 5
independent) that belonged to different chains or owners
and included 5 brands from 4 manufacturers (Figure 2).
The content of 6 of the failed samples was below 90%.
The lowest content was 80.7% and the content of the
approved samples ranged from 90.6% to 104.2% (Figure
3). Interestingly, certain batches of certain brands passed
the content and/or content uniformity tests in some
Figure 2. Distribution of failed samples.
Table 3. Distribution of samples and batches.
Number of samplesa
Brand
code From 36 chain
pharmacies
From 36
independent
pharmacies
Total
Number of
batchesb
Ac 4 4 8 3
Bc 4 3 7 5
Cd 2 0 2 2
Dd 3 4 7 6
Ed 3 7 10 6
Fe 1 0 1 1
Ge 2 0 2 2
Hd 0 1 1 1
Id 6 1 7 5
Jc 1 5 6 4
Kd 3 2 5 3
Le 0 4 4 3
Md 4 6 10 10
Nc 2 0 2 2
Oc 5 1 6 2
Pd 1 4 5 3
Total 41 42 83 57
aA sample is a batch purchased from a single pharmacy. If the same batch is
purchased at another pharmacy, it is considered as a different sample. Dif-
ferent batches of the same brand purchased from the same pharmacy are also
considered as different samples. bThe number of batches of the correspond-
ing brand purchased from all pharmacies without repetition. cManufactured
in Saudi Arabia. dImported from other Arab countries. eImported from Eu-
rope.
pharmacies, but failed in others (Table 4).
The number of target pharmacies in each lot was
greater than the decision value. For this reason, we failed

The Quality of Medicines in Community Pharmacies in Riyadh, Saudi
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516
Figure 3. Content distribution of all samples.
Table 4. Batches that passed in some pharmacie s but faile d in others.
Samples of the same batch
Brand
No. Status
Content uniformity
acceptance value (%)a Average content (%) Pharmacy type
1 Failed 15.66 92.36 Independent
B
2 Passed 07.35 94.74 Independent
1 Failed 19.92 86.81 Independent
D
2 Passed 14.20 91.11 Independent
1 Failed 27.06 84.43 Independent
2 Passed 05.57 95.96 Chain
3 Passed 08.46 95.38 Chain
O
4 Passed 13.21 93.57 Chain
1 Failed 15.08 90.66 Independent
2 Failed 17.24 91.89 Independent
P
3 Passed 08.26 95.41 Independent
aAcceptance value must be ≤15%.
samples in the present work was very low (8%). All
tablet forms passed the quality tests in our study, but
again the significance of this result is uncertain because
of the small percentage of tablets (7%). According to the
SFDA (e-mail communication, Jul 6, 2010), the sales of
tablet forms and European brands in Saudi Arabia during
the second quarter of 2009 amounted to 3.96% and
4.32% of the total sales of amoxicillin (capsules and
tablets), respectively.
to reject the null hypothesis, and both lots were classified
as high-prevalence lots. Thus, our results indicate that
more than 20% of the pharmacies in each lot sell low-
quality amoxicillin, an outcome suggestive of a signi-
ficant problem with important public health implications.
4. Discussion
Substandard samples amounted to 11% of the total
samples, indicating a rather high prevalence of sub-
standard amoxicillin products in CPs in Riyadh. This is
consistent with the findings of Kyriacos et al., although
the sample size for amoxicillin products purchased in
Saudi Arabia was not specified in that study [8]. Like
them, we found that all European samples passed the
quality tests, although the percentage of European
The finding that some samples from the same batch
passed the tests in certain pharmacies, but failed in others,
suggests the occurrence of degradation of the failed
samples, which may originally have been of good quality.
Degradation may have occurred due to poor storage and/
or distribution conditions. The samples were collected
during a very hot season, when the outside temperature

The Quality of Medicines in Community Pharmacies in Riyadh, Saudi
Arabia: A Lot Quality Assurance Sampling (LQAS)-Based Survey
517
in Riyadh during daytime reached approximately 45˚C.
Poor temperature control in the distributors’ facilities,
such as warehouses and delivery vehicles, could have
been resulted in degradation of amoxicillin. Although the
air conditioning in the vast majority of the visited phar-
macies was satisfactory during sampling, the possibility
that the air conditioners had failed or were not in use in
certain pharmacies at certain times cannot be excluded.
However, we cannot exclude poor quality-control prac-
tices during the manufacturing process. This possibility
is supported by the fact that powder in some capsules of
failed samples from one manufacturer was in the form of
a hard mass, possibly formed when the samples dried out
after having absorbed moisture. Thus, poor packaging
may have been a contributory factor.
The average content of the active ingredient in failed
samples was greater than 80%. This value contrasts with
the low value found by Kyriacos et al. (59%) [8].
However, our results seem consistent with the findings of
a study conducted in Indonesia, where 20% of the
amoxicillin tablets analyzed contained an amount of
active ingredient that was only slightly below the accep-
table range according to the British Pharmacopeia (BP)
[22]. Note that in our study two more samples would
have failed the content test (1 sample from each lot),
based on the content range of 92.5% - 110.0% specified
in BP 2012 [32]. The intake of poor-quality antibiotics
may lead to therapeutic failure and the emergence of
bacterial resistance [3].
The number of target pharmacies exceeded the
decision value in both lots (i.e., chain and independent
categories). This finding suggests that intervention
strategies should target both types of CPs. Further, the
unacceptable rate of CPs that sell low-quality medicines
in Riyadh, a capital city where inspection and monitoring
are expected to be relatively strict, suggests that the
situation may be even worse in other cities or more
remote areas of the country. It might be advisable for the
SFDA to perform routine monitoring of wholesalers and
pharmacy storage facilities, distribution facilities, and
environmental conditions inside pharmacies (e.g., tem-
perature, humidity, and exposure to sunlight). In addition,
distributors, pharmacy owners, and pharmacists should
be educated about the possible consequences of failing to
adhere to appropriate distribution and storage conditions
for the provision of medicines.
LQAS proved to be a practical method for surveying
the quality of medicines sold in CPs, using rather small
numbers of pharmacies for sampling, and it may be a
suitable approach for future monitoring by the SFDA or
other investigators in Saudi Arabia, as well as other
countries. The same methodology can be used for follow-
up to monitor changes that may have occurred following
interventions. However, the medicine selected as an
indicator of the quality of medicines may need to be
changed according to the nature of the study or the
geographical area surveyed. In our study, amoxicillin
was selected because it is widely used, widely counter-
feited, and heat-labile (Riyadh is very hot during sum-
mer), and also because substandard amoxicillin was
reported in Saudi Arabia in one study.
5. Limitations
The following limitations may have influenced the re-
sults of this study. First, only capsule and tablet dosage
forms of amoxicillin were sampled. Therefore, the find-
ings cannot necessarily be extended to other dosage
forms or other medicines.
Second, it was not possible to collect samples of a
single batch from each pharmacy because asking the
seller about batches would have revealed that the phar-
macy was under investigation.
Third, samples were analyzed by the chief investigator,
who was not blinded as to the samples being analyzed,
but was blinded as to the pharmacy from which the
sample(s) were obtained. Unintentional expectation bias
might have been introduced because the chief investi-
gator is a Saudi clinical pharmacist. However, this factor
is unlikely to have affected the results of the study,
because there were several samples that failed from
certain pharmacies but passed from others, and because
the samples were repeatedly measured with a validated
method.
Fourth, only content and content uniformity tests were
conducted. Therefore, “quality” in this study refers only
to the acceptable amount and uniformity of the active
ingredient in terms of the ranges specified by the USP.
Finally, because some samples passed the content test
while other samples from the same batch but purchased
from different pharmacies failed it, we assumed that the
failed samples had been degraded. However, we did not
analyze them for degradation products. There are several
methods that can differentiate between degraded and
originally substandard amoxicillin [33,34]. These methods
may be used in future studies.
6. Conclusions
Although this study has several limitations, the results
indicate that there are deficiencies in quality control
within the supply chain (including customs clearance of
imported medicines) and/or in storage facilities in Riyadh,
either at the level of wholesalers or pharmacies, in
addition to possible manufacturing or packaging defects
in some brands of amoxicillin.
LQAS with a mystery shopper provided a readily
reproducible and statistically valid sampling method for

The Quality of Medicines in Community Pharmacies in Riyadh, Saudi
Arabia: A Lot Quality Assurance Sampling (LQAS)-Based Survey
518
investigating the quality of medicines sold at CPs.
Finally, we recommend further studies to investigate
the adherence of CPs, and other facilities in the supply
chain in Riyadh, to optimal conditions for keeping and
selling medicines. Larger-scale randomized surveys
would be helpful to further delineate the scale of the
quality-control problem in CPs.
7. Acknowledgements
The authors would like to thank the Heiwa Nakajima
Foundation (a Japanese nonprofit organization) and the
Prioritized Research Programs at Kanazawa University
for funding. Thanks are also offered to the SFDA for
approving the study and inviting the research team to
Saudi Arabia. The authors especially thank Prof. Saleh A.
Bawazir, Dr. Hajed M. Hashan, Mr. Bassam Alwon, Mr.
Sami Al Sager, and Mr. Adnan Jannadi from the SFDA
and Mr. Abdulrahman Al Sahbi from the Saudi MOH for
all the assistance that they provided in obtaining infor-
mation about pharmacies and medicines. The authors
finally thank the following manufacturers, who res-
ponded to the authenticity check and agreed to allow us
to mention their names: Saudi Pharmaceutical Industries
and Medical Appliances Corporation (Saudi Arabia),
Jazeera Pharmaceutical Industries (Saudi Arabia), The
Arab Pharmaceutical Manufacturing Co. Ltd (Jordan),
Dar Al Dawa Development & Investment Co. Ltd.
(Jordan), and Astellas Pharma Inc. (Japan office).
8. Authors’ Contributions
Research protocol development: HMJK, HP, MA, and
KK. Sampling: HMJK, HP, and KK. Sample analysis
protocol development: HMJK, NY, and KK. Sample
analysis: HMJK. Manuscript draft: HMJK. Manuscript
revision: HMJK, HP, NY, HT, and KK. Obtaining
research funds: HT and KK.
Parts of this study were presented in a poster (Poster
No. 460) at the FIP Centennial Congress of Pharmacy
and Pharmaceutical Sciences, 2012, held in Amsterdam.
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