Accred Qual Assur (2003) 8:231234

DOI 10.1007/s00769-003-0588-x

J. M. F. Nogueira
P. Serdio

Received: 13 June 2002

Accepted: 9 December 2002
Published online: 1 April 2003
Springer-Verlag 2003
J. M. F. Nogueira () P. Serdio
Departamento de Qumica e Bioqumica
da Faculdade de Cincias
da Universidade de Lisboa,
Campo Grande Ed. C8,
1749016 Lisboa, Portugal
e-mail: nogueira@fc.ul.pt
Tel.: +351-21-7500899
Fax: +351-21-7500088
J. M. F. Nogueira
Centro de Cincias Moleculares
e Materiais,
Campo Grande Ed. C8,
1749016 Lisboa, Portugal

PRACTITIONERS REPORT

Determination of the expiration date

of chemical solutions

Abstract Thirty-five chemical solutions, acids, bases, complexing, argentometric, reducing, oxidising,
salts and eluent mixtures, were studied continuously over a 7.5-month
period. Twenty-seven remained reasonably stable and had acceptable
expiration dates, which were equal to
or more than 2 months longer than
the established average deviation of
2% relative to the initial value. Exceptions were made for potassium
permanganate (0.1 M), perchloric acid (0.1 M) and disodium hydrogen
phosphate (10%) solutions, as well
as for HPLC eluent mixtures, which
showed stability with expiration

Introduction
The stability requirements for analytical laboratories demands careful control of the expiration date of chemicals, reagents and solutions. The use of deteriorated or
expired chemical solutions affects the validity of analytical procedures, leading to erroneous data, which can
cause consequences for the community [1].
How can a laboratory establish the expiration dating
of chemical solutions and reagents not provided by suppliers, or for chemical solutions prepared in-house? This
is of increasing concern in analytical laboratories which
follow good laboratory practice (GLP), especially for
those which implement a quality system [2].
The determination of the expiration date of a chemical solution is generally associated with its stability,
which is an intrinsic property affecting the maintenance
of the functional capacity of the reagent for a particular
analytical application. In the laboratory, the stability of
reagents and solutions should be checked just before use

dates equal to stated values or shorter by 1 month. The eight chemical

solutions presenting expiration dating higher than 6 months were hydrochloric acid (0.1 and 1 M), sulphuric acid (0.5 and 1.5 M), ethylenediamine tetraacetic acid (EDTA)
(0.1 M), silver nitrate (0.1 M), ammonium thiocyanate (0.1 M) and iodine (0.1 M). The present data is a
suitable guideline for the date of several chemical solutions routinely
used in the analytical laboratories.
Keywords Date Chemical
solutions Stability Shelf-life
Chemical analysis

and regularly at routine intervals. Each time a bottle is

opened, the reagent or solution is exposed to various external influences that may alter its integrity for a specific
use.
Some reagents and solutions, e.g. sodium hydroxide,
easily react with carbon dioxide in the atmosphere. Temperature, light, air, moisture and storage bottle material,
etc. can also affect the physical appearance of the chemical solutions (easily recognizable as a colour change)
sedimentation and chemical decomposition, leading
sometimes to an erroneous concentration. On the other
hand, the number of times a bottle is opened and for how
long are factors which may also influence the stability of
the chemical solutions.
Shelf-life is defined as the period of time a product is
considered usable for each application taking into account physical and/or chemical changes. Products considered to have extensive shelf-life when stored unopened and under the proper conditions are not given an
expiration date. To clarify a common misconception, no

232

expiration date and forever are not synonymous. The

expiration date may be understood as the date at/or after
which the chemical solution may no longer be stable for
a specific analytical application.
Taking in consideration a wide range of applications,
the expiration date of a chemical solution should be established on the basis of their specific use. Some solutions may be too old for one analytical application, but
still suitable for another. For example, a sodium hydroxide solution used to standardize hydrochloric acid solutions may have reached its expiration date for this type
of application, but it would still be suitable to adjust pH
of acids prior to disposal, a less critical application. In
this context, laboratories should establish their own internal standard operating procedures (SOPs) for the replacement of chemical solutions after a specific period
of time.
An expiration date should be assigned to each type of
chemical solutions, i.e. acids, bases, complexing, argentometric, reducing, oxidising, salts, mixture of solvents, etc. For most reagents, with the exception of those
with a manufacturer-specified expiration date, a colour
code system may be also implemented to better identify
expiration dates [3].
Chemical solutions are used for a wide variety of applications. Users should assess a chemical solution for its
actual expiration date based on the application for which
the chemical or reagent is being used, taking into consideration the time spend on preparation and the associated
costs, as a policy to improve laboratory performance. In
this context, there is no information in the literature regarding expiration dating of chemical solutions used in
analytical laboratories.
The aim of the present work was to evaluate the expiration date of several chemical solutions in common use,
particularly in pharmaceutical laboratories, in order to
establish a suitable guideline for analytical departments.

Table 1 Typical reactions involved in the titrimetric procedures adopted in the present
study [4, 5, 6, 7, 8, 9]

Acids
Bases
Complexing
Argentometric
Reducing
Oxidizing

a Titrators in italics
b Acetic medium

Experimental
In the present study calibrated glass material was used
and all the reagents were analytical grade. The solutions
were stored in amber glass bottles. Plastic bottles were
used only for salt solutions. The bottles were opened exclusively for analytical purposes and kept in a closed
cabinet, protected from light, at room temperature
(20 C).
The solutions were studied by means of frequency of
use and application demand, and rigorous concentration,
such as acidic (HCl, H2SO4 and HClO4), basic (NaOH
and NH3), complexing (ethylenediamine tetraacetic acid
EDTA; C10H16N2O8), argentometric (AgNO3 and
NH4SCN), reducing (Na2S2O3), oxidising (I2 and
KMnO4), salts (NH4CH3COO, (NH4)2HPO4, K2HPO4,
KH2PO4, Na2HPO4, NaH2PO4, NaCl and Na2SO4) and
eluent mixtures (CH3OH/H2O, CH3CH2OH/H2O and
CH3CN/H2O) for high performance liquid chromatography (HPLC).
The expiration date was studied by the periodic determination of the concentration of each solution. Titrimetric procedures were employed to analyse acidic, basic,
complexing, argentometric, reducing and oxidizing solutions. Table 1 shows the main reactions involved in the
titrimetric procedures.
Ion-exchange chromatography was used to analyse
salt solutions, using a Dionex DX-500, with a quaternary
pump (GP40), cationic and anionic suppressor columns
(CSRS-I, 4 mm and ASRS-I, 4 mm), a conductivity detector (CD20), a column (IonPac CS12; AS4A,
2504 mm) and a pre-column (IonPac AG4, 504 mm).
For cationic (Na+ and K+) and anionic (CH3COO, SO42
and PO43) determination, methane sulphonic acid
(0.02 M) and carbonate/bicarbonate (0.02 M/0.02 M) solutions were used as mobile phases having flow rates of
1.0 and 1.3 ml/min, respectively. Karl-Fisher (Metrohm

Chemical
solutions

Main reactionsa

HCl
H2SO4
HClO4b
NaOH
NH3

Na2CO3(aq)+2HCl(aq)2NaCl(aq)+H2CO3(aq)
Na2CO3(aq)+H2SO4(aq)Na2SO4(aq)+H2CO3(aq)
KHC8H4O4(ac)+HClO4(ac)H2C8H4O4(ac)+KClO4(ac)
KHC8H4O4(aq)+NaOH(aq)NaKC8H4O4(aq)+H2O(l)
HCl(aq)+NH3(aq)NH4Cl(aq)
NaOH(aq)+HCl(aq)NaCl(aq)+H2O(l)(back titration)
Ca2+(aq)+Y4(aq)CaY2(aq)
NaCl(aq)+AgNO3(aq)AgCl(s)+NaNO3(aq)
Ag+(aq) + SCN-(aq) AgSCN(s)
BrO3(aq)+9I(aq)+6H+(aq)Br(aq)+3I3(aq)+3H2O(l)
I3(aq)+2S2O32(aq)3I(aq)+S4O62(aq) (back titration)
H3AsO3(aq)+I3(aq)+H2O(l)H3AsO4(aq)+2H+(aq)+3I(aq)
5C2O42(aq)+2MnO4(aq)+16H+(aq)10CO2(g)+2Mn2+(aq)+8H2O(l)

EDTA (Y4)
AgNO3
NH4SCN
Na2S2O3
I 3
KMnO4

233

720 KFS Trinitro) was used to analyse the composition

of the HPLC eluent mixtures.
All analytical procedures employed were based and
validated according to American (USP) and British (BP)
Pharmacopoeias or in agreement with GLP procedures [4,
5, 6, 7, 8, 9]. The uncertainty of titrimetric (<0.25%),
chromatographic (<0.60%) and Karl-Fisher (<0.36%) procedures were calculated according to the EURACHEM/
CIAC Guide [10].
The solutions were analysed weekly during the first
month and then monthly over a 7.5-month period , where
three assays and a blank were performed each time a solution was studied. In some cases, to cover a wide range
of concentrations, the study of a higher and a lower concentration was performed, assuming that all the solutions
of intermediate concentration would have the lower observed expiration date .
The expiration date of each chemical solution studied
was establish on the basis of the average deviations systematically higher than 2% relative to the initial value, obtained by standardization. It was also established, if deterioration signs occurred, e.g. colour changes or sedimentation,
the solutions were percolated before standardization. If
those signs reminded, the study was concluded and the solution rejected. The period until those occurrences was assumed to be the expiration dating for those solutions.

Fig. 1 Diagram showing the expiration dating for the acidic, basic, complexing, argentometric, reducing and oxidizing solutions
studied

Results and discussion

To assign an expiration date to each of the chemical solution studied, an average deviation systematically higher than 2% relative to the initial value was established.
This criteria was established taking into consideration
the uncertainty usually accepted as GLP by analytical
departments to reject solutions outside of the expected
concentration, due the external influences. Therefore, the
average deviation established (2%) is an overestimate
when compared with the initial value () of each chemical solution: a 3 confidence bands would include
99.74% of Gaussian data.
From the 35 chemical solutions studied continuously
over the 7.5-month period, Fig. 1 shows the expiration
dating behaviour for the acidic, basic, complexing, argentometric, reducing and oxidizing solutions, some of
them having more than one concentration level.
The acidic solutions of chloridric (0.1 and 1 M) and
sulphuric acids (0.5 and 1.5 M) reminded stable over
7 months, showing a similar behaviour within the established average deviation of 2% in relation to the initial
concentration, whereas perchloric acid (0.1 M) presented
an expiration dating of only 1 month. In general, the
more diluted solutions presented a decreasing stability in
relation to the initial concentration, where the lower
acidic content of the solutions suggests a higher vulnerability to external factors.

Fig. 2 Shewart chart showing the average relative deviation observed for ethylenediamine tetraacetic acid (EDTA) solutions
(0.01 and 0.1 M) studied over a 7.5-month period

The basic solutions, such as sodium hydroxide (0.2

and 5 M) and ammonia (5 and 10 M), proved to be sensitive to atmospheric carbon dioxide and presented an expiration date of 5 and 3 months, respectively.
The EDTA-complexing solutions seemed to lose
some stability during the present study, as observed in
Fig. 1. Although the 0.1 M solution remain very stable
over the 7.5 months, the 0.01 M solutions become unstable after 2 months. The Shewart chart from Fig. 2, exemplifies the degradation kinetics profile for both EDTA
solutions within the established average deviation of
2%, relative to the initial concentration. A clear systematic deviation could be observed after 2 months for
the 0.01 M EDTA solution, which confirms once again
that the lower the concentration the higher the susceptibility to external factors.
Chemical solutions used for argentometric procedures, such as 0.1 M silver nitrate, showed an expiration

234

Fig. 3 Diagram showing the expiration dating for the salt solutions and HPLC eluent mixtures studied

dating of 7 months. Nevertheless, for lower concentrations (0.01 M) the stability decreased to 5 months, due
probably to the much higher incidence of photochemical
degradation. For the 0.1 M ammonium thiocyanate solution, usually used for back-titration, an expiration dating
of 7 months was achieved.
The redox chemicals, like the reducing solution 0.1 M
sodium thiosulphate, showed a expiration dating of
5 months within the deviation establish. Unexpectedly, the
oxidizing solution, 0.1 M iodine, presented a long expiration date of 7.5 months; 5 months for a 0.01 M solution.
The lack of stability of the iodine solutions, due to volatility and air-oxidation processes, presented, as expected, a
low shelf-life. Nevertheless, the low frequency of use of
iodine solutions, observed in analytical laboratories in relation to other chemicals, accented the importance of a
long expiration date. The 0.1 M potassium permanganate
solutions also showed low stability, showing expiration
dating of only 1 month, probably owing to the occurrence
of photo degradation and air-oxidation reactions.
Figure 3 shows the expiration dating behaviour for
aqueous salt solutions and eluent mixtures currently used
in HPLC. In general, the salt solutions studied showed
an expiration dating equal to or longer than 5 months:
2 M ammonium acetate, 0.03 M diammonium hydrogen

phosphate, sodium dihydrogen phosphate (0.05 and

0.1 M), sodium chloride (5 ppm and 0.1 M) and sulphate
(10 ppm). Exceptions were observed for disodium hydrogen phosphate (10%, w/v), potassium dihydrogen
phosphate (0.01 and 1 M) and dipotassium hydrogen
phosphate (0.01 and 0.2 M), showing expiration dates
lower than 1 and 4 months, respectively. The 10% disodium hydrogen phosphate solutions showed a very high
instability and it is advisable to always use a fresh solution for analytical purposes.
The HPLC eluent mixtures (v/v), methanol/water
(75/25 and 35/65), ethanol/water (30/70) and acetonitrile/water (20/80 and 90/10), presented an expiration
dating of only 1 month, showing some instability behaviour for the established average deviation of 2% relative to the initial composition.
In summary, from the 35 chemical solutions studied
over the 7.5-month period, 27 remained reasonably stable and had suitable expiration dates, equal or longer
than 2 months for the established average deviation of
2% in relation to the initial concentration. Exceptions
are made for potassium permanganate (0.1 M), perchloric acid (0.1 M) and disodium hydrogen phosphate
(10%) solutions, as well as for HPLC eluent mixtures,
which showed stability with expiration dates equal to or
shorter than 1 month. The top 8 chemical solutions that
presented expiration dating longer than 6 months were
hydrochloric acid (0.1 and 1 M), sulphuric acid (0.5 and
1.5 M), EDTA (0.1 M), silver nitrate (0.1 M), ammonium thiocyanate (0.1 M) and iodine (0.1 M).
From the present work, its obvious that real solutions
used in the laboratory are often opened much more frequently and for longer periods of time than in the present
study, where the external factors should have a more
substantial influence in the overall expiration dating.
Nevertheless, the data obtained must be understood as a
guideline to the expiration dating of several chemical solutions used for analytical purposes that could bring several benefits, enhancing laboratorys performance.
Acknowledgements The authors acknowledge the financial support of Hovione SA, R. Agudo for technical assistance and Prof.
Dinis Pestana for statistics helpful.

References
1. Prichard E (1995) Quality in the analytical chemistry laboratory. Wiley, UK
2. Lawn RE, Thompson M, Walker RF
(1997) Proficiency testing in analytical
chemistry. The Royal Society of Chemistry, UK
3. Garner WE, Barge MS, Ussuary JP
(1992) Good laboratory practice. ACS,
Washington D.C., USA

4. Serdio P (2001) Validation of the stability of solutions, Report AA/RE181,

Hovione SA, FCUL, Portugal
5. (1985) United States Pharmacopoeia,
Vol. XXI
6. (1990) United States Pharmacopoeia,
Vol. XXII
7. (1995) United States Pharmacopoeia,
Vol. XXIII

8. (1980) British Pharmacopoeia, A45,

Vol. I
9. (1988) British Pharmacopoeia, Vol. I
10. EURACHEM/CITAC (2000) Quantifying uncertainty in analytical measurement, EURACHEM/CITAC Guide 2nd
edn. EURACHEM/CITAC, Teddington, UK