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Determination of the expiration date of chemical solutions

Article in Accreditation and Quality Assurance · May 2003

DOI: 10.1007/s00769-003-0588-x

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Accred Qual Assur (2003) 8:231–234
DOI 10.1007/s00769-003-0588-x PRACTITIONER’S REPORT

J. M. F. Nogueira Determination of the expiration date

P. Serôdio
of chemical solutions

Received: 13 June 2002 Abstract Thirty-five chemical solu- dates equal to stated values or short-
Accepted: 9 December 2002 tions, acids, bases, complexing, ar- er by 1 month. The eight chemical
Published online: 1 April 2003 gentometric, reducing, oxidising, solutions presenting expiration dat-
© Springer-Verlag 2003 salts and eluent mixtures, were stud- ing higher than 6 months were hy-
ied continuously over a 7.5-month drochloric acid (0.1 and 1 M), sul-
J. M. F. Nogueira (✉) · P. Serôdio period. Twenty-seven remained rea- phuric acid (0.5 and 1.5 M), ethyl-
Departamento de Química e Bioquímica sonably stable and had acceptable enediamine tetraacetic acid (EDTA)
da Faculdade de Ciências
da Universidade de Lisboa, expiration dates, which were equal to (0.1 M), silver nitrate (0.1 M), am-
Campo Grande Ed. C8, or more than 2 months longer than monium thiocyanate (0.1 M) and io-
1749–016 Lisboa, Portugal the established average deviation of dine (0.1 M). The present data is a
e-mail: [email protected] ±2% relative to the initial value. Ex- suitable guideline for the date of sev-
Tel.: +351-21-7500899 ceptions were made for potassium eral chemical solutions routinely
Fax: +351-21-7500088
permanganate (0.1 M), perchloric ac- used in the analytical laboratories.
J. M. F. Nogueira id (0.1 M) and disodium hydrogen
Centro de Ciências Moleculares
e Materiais, phosphate (10%) solutions, as well Keywords Date · Chemical
Campo Grande Ed. C8, as for HPLC eluent mixtures, which solutions · Stability · Shelf-life ·
1749–016 Lisboa, Portugal showed stability with expiration Chemical analysis

Introduction and regularly at routine intervals. Each time a bottle is

opened, the reagent or solution is exposed to various ex-
The stability requirements for analytical laboratories de- ternal influences that may alter its integrity for a specific
mands careful control of the expiration date of chemi- use.
cals, reagents and solutions. The use of deteriorated or Some reagents and solutions, e.g. sodium hydroxide,
expired chemical solutions affects the validity of analyti- easily react with carbon dioxide in the atmosphere. Tem-
cal procedures, leading to erroneous data, which can perature, light, air, moisture and storage bottle material,
cause consequences for the community [1]. etc. can also affect the physical appearance of the chemi-
How can a laboratory establish the expiration dating cal solutions (easily recognizable as a colour change)
of chemical solutions and reagents not provided by sup- sedimentation and chemical decomposition, leading
pliers, or for chemical solutions prepared in-house? This sometimes to an erroneous concentration. On the other
is of increasing concern in analytical laboratories which hand, the number of times a bottle is opened and for how
follow good laboratory practice (GLP), especially for long are factors which may also influence the stability of
those which implement a quality system [2]. the chemical solutions.
The determination of the expiration date of a chemi- Shelf-life is defined as the period of time a product is
cal solution is generally associated with its stability, considered usable for each application taking into ac-
which is an intrinsic property affecting the maintenance count physical and/or chemical changes. Products con-
of the functional capacity of the reagent for a particular sidered to have extensive shelf-life when stored un-
analytical application. In the laboratory, the stability of opened and under the proper conditions are not given an
reagents and solutions should be checked just before use expiration date. To clarify a common misconception, “no
232

expiration date” and “forever” are not synonymous. The Experimental

expiration date may be understood as the date at/or after
which the chemical solution may no longer be stable for In the present study calibrated glass material was used
a specific analytical application. and all the reagents were analytical grade. The solutions
Taking in consideration a wide range of applications, were stored in amber glass bottles. Plastic bottles were
the expiration date of a chemical solution should be es- used only for salt solutions. The bottles were opened ex-
tablished on the basis of their specific use. Some solu- clusively for analytical purposes and kept in a closed
tions may be too old for one analytical application, but cabinet, protected from light, at room temperature
still suitable for another. For example, a sodium hydrox- (20 °C).
ide solution used to standardize hydrochloric acid solu- The solutions were studied by means of frequency of
tions may have reached its expiration date for this type use and application demand, and rigorous concentration,
of application, but it would still be suitable to adjust pH such as acidic (HCl, H2SO4 and HClO4), basic (NaOH
of acids prior to disposal, a less critical application. In and NH3), complexing (ethylenediamine tetraacetic acid
this context, laboratories should establish their own in- – EDTA; C10H16N2O8), argentometric (AgNO3 and
ternal standard operating procedures (SOPs) for the re- NH4SCN), reducing (Na2S2O3), oxidising (I2 and
placement of chemical solutions after a specific period KMnO4), salts (NH4CH3COO, (NH4)2HPO4, K2HPO4,
of time. KH2PO4, Na2HPO4, NaH2PO4, NaCl and Na2SO4) and
An expiration date should be assigned to each type of eluent mixtures (CH3OH/H2O, CH3CH2OH/H2O and
chemical solutions, i.e. acids, bases, complexing, ar- CH3CN/H2O) for high performance liquid chromatogra-
gentometric, reducing, oxidising, salts, mixture of sol- phy (HPLC).
vents, etc. For most reagents, with the exception of those The expiration date was studied by the periodic deter-
with a manufacturer-specified expiration date, a colour mination of the concentration of each solution. Titrimet-
code system may be also implemented to better identify ric procedures were employed to analyse acidic, basic,
expiration dates [3]. complexing, argentometric, reducing and oxidizing solu-
Chemical solutions are used for a wide variety of ap- tions. Table 1 shows the main reactions involved in the
plications. Users should assess a chemical solution for its titrimetric procedures.
actual expiration date based on the application for which Ion-exchange chromatography was used to analyse
the chemical or reagent is being used, taking into consid- salt solutions, using a Dionex DX-500, with a quaternary
eration the time spend on preparation and the associated pump (GP40), cationic and anionic suppressor columns
costs, as a policy to improve laboratory performance. In (CSRS-I, 4 mm and ASRS-I, 4 mm), a conductivity de-
this context, there is no information in the literature re- tector (CD20), a column (IonPac CS12; AS4A,
garding expiration dating of chemical solutions used in 250×4 mm) and a pre-column (IonPac AG4, 50×4 mm).
analytical laboratories. For cationic (Na+ and K+) and anionic (CH3COO−, SO42−
The aim of the present work was to evaluate the expi- and PO43−) determination, methane sulphonic acid
ration date of several chemical solutions in common use, (0.02 M) and carbonate/bicarbonate (0.02 M/0.02 M) so-
particularly in pharmaceutical laboratories, in order to lutions were used as mobile phases having flow rates of
establish a suitable guideline for analytical departments. 1.0 and 1.3 ml/min, respectively. Karl-Fisher (Metrohm

Table 1 Typical reactions in-

volved in the titrimetric proce- Chemical Main reactionsa
dures adopted in the present solutions
study [4, 5, 6, 7, 8, 9]
Acids HCl Na2CO3(aq)+2HCl(aq)→2NaCl(aq)+H2CO3(aq)
H2SO4 Na2CO3(aq)+H2SO4(aq)→Na2SO4(aq)+H2CO3(aq)
HClO4b KHC8H4O4(ac)+HClO4(ac)→H2C8H4O4(ac)+KClO4(ac)
Bases NaOH KHC8H4O4(aq)+NaOH(aq)→NaKC8H4O4(aq)+H2O(l)
NH3 HCl(aq)+NH3(aq)→NH4Cl(aq)
NaOH(aq)+HCl(aq)→NaCl(aq)+H2O(l)(back titration)
Complexing EDTA (Y4−) Ca2+(aq)+Y−4(aq)→CaY2−(aq)
Argentometric AgNO3 NaCl(aq)+AgNO3(aq)→AgCl(s)+NaNO3(aq)
NH4SCN Ag+(aq) + SCN-(aq) → AgSCN(s)
Reducing Na2S2O3 BrO3−(aq)+9I−(aq)+6H+(aq)→Br−(aq)+3I3−(aq)+3H2O(l)
I3−(aq)+2S2O32−(aq)→3I−(aq)+S4O62−(aq) (back titration)
Oxidizing I 3− H3AsO3(aq)+I3−(aq)+H2O(l)→H3AsO4(aq)+2H+(aq)+3I−(aq)
a Titrators in italics
b Acetic medium
KMnO4 5C2O42−(aq)+2MnO4−(aq)+16H+(aq)→10CO2(g)+2Mn2+(aq)+8H2O(l)
 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%) pro-
cedures 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 so-
lution was studied. In some cases, to cover a wide range
of concentrations, the study of a higher and a lower con-
centration was performed, assuming that all the solutions
of intermediate concentration would have the lower ob-
served expiration date .
The expiration date of each chemical solution studied Fig. 1 Diagram showing the expiration dating for the acidic, ba-
sic, complexing, argentometric, reducing and oxidizing solutions
was establish on the basis of the average deviations system- studied
atically higher than ±2% relative to the initial value, ob-
tained by standardization. It was also established, if deterio-
ration signs occurred, e.g. colour changes or sedimentation,
the solutions were percolated before standardization. If
those signs reminded, the study was concluded and the so-
lution rejected. The period until those occurrences was as-
sumed to be the expiration dating for those solutions.

Results and discussion

To assign an expiration date to each of the chemical so-
lution studied, an average deviation systematically high-
er than ±2% relative to the initial value was established.
This criteria was established taking into consideration
the uncertainty usually accepted as GLP by analytical Fig. 2 Shewart chart showing the average relative deviation ob-
served for ethylenediamine tetraacetic acid (EDTA) solutions
departments to reject solutions outside of the expected (0.01 and 0.1 M) studied over a 7.5-month period
concentration, due the external influences. Therefore, the
average deviation established (±2%) is an overestimate
when compared with the initial value (µ) of each chemi- The basic solutions, such as sodium hydroxide (0.2
cal solution: a µ±3σ confidence bands would include and 5 M) and ammonia (5 and 10 M), proved to be sensi-
99.74% of Gaussian data. tive to atmospheric carbon dioxide and presented an ex-
From the 35 chemical solutions studied continuously piration date of 5 and 3 months, respectively.
over the 7.5-month period, Fig. 1 shows the expiration The EDTA-complexing solutions seemed to lose
dating behaviour for the acidic, basic, complexing, ar- some stability during the present study, as observed in
gentometric, reducing and oxidizing solutions, some of Fig. 1. Although the 0.1 M solution remain very stable
them having more than one concentration level. over the 7.5 months, the 0.01 M solutions become unsta-
The acidic solutions of chloridric (0.1 and 1 M) and ble after 2 months. The Shewart chart from Fig. 2, exem-
sulphuric acids (0.5 and 1.5 M) reminded stable over plifies the degradation kinetics profile for both EDTA
7 months, showing a similar behaviour within the estab- solutions within the established average deviation of
lished average deviation of ±2% in relation to the initial ±2%, relative to the initial concentration. A clear sys-
concentration, whereas perchloric acid (0.1 M) presented tematic deviation could be observed after 2 months for
an expiration dating of only 1 month. In general, the the 0.01 M EDTA solution, which confirms once again
more diluted solutions presented a decreasing stability in that the lower the concentration the higher the suscepti-
relation to the initial concentration, where the lower bility to external factors.
acidic content of the solutions suggests a higher vulnera- Chemical solutions used for argentometric proce-
bility to external factors. dures, such as 0.1 M silver nitrate, showed an expiration
234

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 hy-
drogen 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% diso-
dium hydrogen phosphate solutions showed a very high
instability and it is advisable to always use a fresh solu-
tion for analytical purposes.
The HPLC eluent mixtures (v/v), methanol/water
(75/25 and 35/65), ethanol/water (30/70) and acetoni-
trile/water (20/80 and 90/10), presented an expiration
dating of only 1 month, showing some instability behav-
iour for the established average deviation of ±2% rela-
Fig. 3 Diagram showing the expiration dating for the salt solu-
tions and HPLC eluent mixtures studied tive to the initial composition.
In summary, from the 35 chemical solutions studied
over the 7.5-month period, 27 remained reasonably sta-
dating of 7 months. Nevertheless, for lower concentra- ble and had suitable expiration dates, equal or longer
tions (0.01 M) the stability decreased to 5 months, due than 2 months for the established average deviation of
probably to the much higher incidence of photochemical ±2% in relation to the initial concentration. Exceptions
degradation. For the 0.1 M ammonium thiocyanate solu- are made for potassium permanganate (0.1 M), perchlo-
tion, usually used for back-titration, an expiration dating ric acid (0.1 M) and disodium hydrogen phosphate
of 7 months was achieved. (10%) solutions, as well as for HPLC eluent mixtures,
The redox chemicals, like the reducing solution 0.1 M which showed stability with expiration dates equal to or
sodium thiosulphate, showed a expiration dating of shorter than 1 month. The top 8 chemical solutions that
5 months within the deviation establish. Unexpectedly, the presented expiration dating longer than 6 months were
oxidizing solution, 0.1 M iodine, presented a long expira- hydrochloric acid (0.1 and 1 M), sulphuric acid (0.5 and
tion date of 7.5 months; 5 months for a 0.01 M solution. 1.5 M), EDTA (0.1 M), silver nitrate (0.1 M), ammoni-
The lack of stability of the iodine solutions, due to volatil- um thiocyanate (0.1 M) and iodine (0.1 M).
ity and air-oxidation processes, presented, as expected, a From the present work, it’s obvious that real solutions
low shelf-life. Nevertheless, the low frequency of use of used in the laboratory are often opened much more fre-
iodine solutions, observed in analytical laboratories in re- quently and for longer periods of time than in the present
lation to other chemicals, accented the importance of a study, where the external factors should have a more
long expiration date. The 0.1 M potassium permanganate substantial influence in the overall expiration dating.
solutions also showed low stability, showing expiration Nevertheless, the data obtained must be understood as a
dating of only 1 month, probably owing to the occurrence guideline to the expiration dating of several chemical so-
of photo degradation and air-oxidation reactions. lutions used for analytical purposes that could bring sev-
Figure 3 shows the expiration dating behaviour for eral benefits, enhancing laboratory’s performance.
aqueous salt solutions and eluent mixtures currently used
in HPLC. In general, the salt solutions studied showed Acknowledgements The authors acknowledge the financial sup-
an expiration dating equal to or longer than 5 months: port of Hovione SA, R. Agudo for technical assistance and Prof.
2 M ammonium acetate, 0.03 M diammonium hydrogen Dinis Pestana for statistics helpful.

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