using several types of detectors although those of MS/MS are the most used [5, 7, 17,
19, 24, 28, 30, 42, 47, 50, 51, 57, 60, 69, 71–73, 78, 80, 81, 83, 84, 103, 107,
110]. Less frequently, HPLC-MS is used [4, 13, 105]. UV (UV) and UV diode array
(DAD) spectrophotometric detectors are used alone (HPLC-UV) [55, 61, 89, 95,
109, 115], (HPLC-DAD) [8, 43, 45, 86, 91, 92, 96, 102, 104] or are combined with
MS (HPLC-DAD-MS [43, 105], HPLC-UV-MS/MS [65]. Fluorescence detectors
(FI) [102] are also used. The advent of ultra HPLC (UPLC), which allows operating
at pressures much higher than normal HPLC, has made it possible to significantly
shorten the analysis times (~10 min), improve resolution, and minimize the matrixassociated effects [13, 57, 65, 103, 111, 123].
HPLC-MS/MS HPLC-MS/MS is a sensitive, selective technique that allows to
analyze concentrations in the order of ngL
À1 and less, but unlike GC, it requires an
interface for the introduction of the sample into the MS detector. The interface
mostly used for polar molecules, such as NSAIDs, is electrospray ionization (ESI)
[17, 19, 24, 28, 42, 43, 47, 50, 57, 60, 63, 69, 71–73, 78, 81, 84, 103, 105, 107,
110]. This interface ionizes in solution by evaporation of electrically charged drops
that are obtained by nebulization. It can work in positive or negative ion modes
[43, 60, 69, 83, 88, 104, 105, 110] or in multiple separation mode (MRM) [7, 17, 19,
24, 28, 42, 50, 57, 63, 65, 69, 71, 72, 78, 80, 81, 84, 103, 107], which allows
collection of positive or negative ions depending on the analytes to be detected.
NSAIDs are best detected in negative mode [7, 17, 19, 57]. The atmospheric
pressure chemical ionization interface (APCI), which ionizes in the gas phase, is
less used [30, 110].
The columns most commonly used in HPLC or UPLC equipment for the determination of NSAIDs in water samples are reverse phase type C 18 [7, 17, 19, 24, 28,
43, 45, 50, 57, 60, 63, 69, 71–73, 80, 83, 84, 86, 91, 105, 121] or C 8 [17, 81, 91] of
different sizes and diameters. The mostly used diameter is 2 μm. In order to adjust
the pH of the mobile phase, formic acid [7, 19, 50, 65, 69, 73, 91, 103, 107, 110]
acetic acid [42, 50, 55, 60, 78], ammonium hydroxide [24, 28, 84], and ammonium
acetate [7, 50, 69, 73] have been used. The mobile phase uses methanol [17, 42, 50,
65, 69, 71, 73, 78, 83, 110], acetonitrile [7, 24, 28, 57, 80, 84, 103, 107], or
combinations thereof [19, 47, 60, 91]. In order to improve detection sensitivity,
tri-n-butyl amine (TrBA) [7, 42, 50, 78] and butylammonium acetate [7] are used.
High-purity N 2 is used as a nebulizing gas [17, 19, 28, 42, 47, 50, 71, 84, 103] and as
a carrier gas [17, 19, 50], although, for the latter purpose, Ar is more frequently used
[28, 71, 103, 110, 121].
MS coupled to HPLC for tandem spectrometry is generally the triple quadrupole
method [7, 17, 28, 42, 50, 57, 60, 68, 71, 72, 80, 81, 84, 103, 107] although ion traps
have also been used [24]. The sources of ions are desorption and non-gaseous,
similar to those used in GC.
HPLC-DAD HPLC-DAD is used when the expected concentrations of analytes are
in the order of μgL
À1 [8, 43, 65, 86, 91, 96, 102, 104] as occurs in plant effluents.
The columns can be C 18 [8, 86, 91, 92, 102, 109], C 30 [91], or C 16 [104]. The most
Quantification of Non-steroidal Anti-inflammatory Drug in Water
97
19, 24, 28, 30, 42, 47, 50, 51, 57, 60, 69, 71–73, 78, 80, 81, 83, 84, 103, 107,
110]. Less frequently, HPLC-MS is used [4, 13, 105]. UV (UV) and UV diode array
(DAD) spectrophotometric detectors are used alone (HPLC-UV) [55, 61, 89, 95,
109, 115], (HPLC-DAD) [8, 43, 45, 86, 91, 92, 96, 102, 104] or are combined with
MS (HPLC-DAD-MS [43, 105], HPLC-UV-MS/MS [65]. Fluorescence detectors
(FI) [102] are also used. The advent of ultra HPLC (UPLC), which allows operating
at pressures much higher than normal HPLC, has made it possible to significantly
shorten the analysis times (~10 min), improve resolution, and minimize the matrixassociated effects [13, 57, 65, 103, 111, 123].
HPLC-MS/MS HPLC-MS/MS is a sensitive, selective technique that allows to
analyze concentrations in the order of ngL
À1 and less, but unlike GC, it requires an
interface for the introduction of the sample into the MS detector. The interface
mostly used for polar molecules, such as NSAIDs, is electrospray ionization (ESI)
[17, 19, 24, 28, 42, 43, 47, 50, 57, 60, 63, 69, 71–73, 78, 81, 84, 103, 105, 107,
110]. This interface ionizes in solution by evaporation of electrically charged drops
that are obtained by nebulization. It can work in positive or negative ion modes
[43, 60, 69, 83, 88, 104, 105, 110] or in multiple separation mode (MRM) [7, 17, 19,
24, 28, 42, 50, 57, 63, 65, 69, 71, 72, 78, 80, 81, 84, 103, 107], which allows
collection of positive or negative ions depending on the analytes to be detected.
NSAIDs are best detected in negative mode [7, 17, 19, 57]. The atmospheric
pressure chemical ionization interface (APCI), which ionizes in the gas phase, is
less used [30, 110].
The columns most commonly used in HPLC or UPLC equipment for the determination of NSAIDs in water samples are reverse phase type C 18 [7, 17, 19, 24, 28,
43, 45, 50, 57, 60, 63, 69, 71–73, 80, 83, 84, 86, 91, 105, 121] or C 8 [17, 81, 91] of
different sizes and diameters. The mostly used diameter is 2 μm. In order to adjust
the pH of the mobile phase, formic acid [7, 19, 50, 65, 69, 73, 91, 103, 107, 110]
acetic acid [42, 50, 55, 60, 78], ammonium hydroxide [24, 28, 84], and ammonium
acetate [7, 50, 69, 73] have been used. The mobile phase uses methanol [17, 42, 50,
65, 69, 71, 73, 78, 83, 110], acetonitrile [7, 24, 28, 57, 80, 84, 103, 107], or
combinations thereof [19, 47, 60, 91]. In order to improve detection sensitivity,
tri-n-butyl amine (TrBA) [7, 42, 50, 78] and butylammonium acetate [7] are used.
High-purity N 2 is used as a nebulizing gas [17, 19, 28, 42, 47, 50, 71, 84, 103] and as
a carrier gas [17, 19, 50], although, for the latter purpose, Ar is more frequently used
[28, 71, 103, 110, 121].
MS coupled to HPLC for tandem spectrometry is generally the triple quadrupole
method [7, 17, 28, 42, 50, 57, 60, 68, 71, 72, 80, 81, 84, 103, 107] although ion traps
have also been used [24]. The sources of ions are desorption and non-gaseous,
similar to those used in GC.
HPLC-DAD HPLC-DAD is used when the expected concentrations of analytes are
in the order of μgL
À1 [8, 43, 65, 86, 91, 96, 102, 104] as occurs in plant effluents.
The columns can be C 18 [8, 86, 91, 92, 102, 109], C 30 [91], or C 16 [104]. The most
Quantification of Non-steroidal Anti-inflammatory Drug in Water
97