sadecka-et-al-_-2001.pdf

Journal of Pharmaceutical and Biomedical Analysis25 (2001) 881891

Determination of ibuprofen and naproxen in tablets

Jana Sadecka, Miroslav C akrt, Andrea Hercegova, Jozef Polonsky *,Ivan Skacani

Department of Analytical Chemistry, Faculty of Chemical Technology, Sloak Uniersity of Technology, Radlinskeho 9,SK-812 37 Bratislaa, Sloak Republic

Received 7 October 2000; received in revised form 7 December 2000; accepted 29 December 2000

Abstract

Ibuprofen and naproxen have been quantified in tablets by capillary isotachophoresis. Hydrochloric acid (10mmol/l) adjusted with creatinine to pH 5.0 plus 0.1% polyvinylpyrrolidone was used as the leading electrolyte and 10mmol/l 4-morpholineethanesulfonic acid as the terminating electrolyte. Linearity was observed from 40.0 to 200.0mg/l of ibuprofen (naproxen), with a coefficient of determination (r2) of 0.999. Good quantitation was obtained inshort analysis time. The isotachophoretic results were compared with those obtained by the fluorescence spectrometry.Experimental parameters for ibuprofen were: EX=224 nm and EM=290 nm. Experimental parameters fornaproxen were: EX=230 nm and EM=355 nm. The calibration plot was found to be linear in the range 0.42.4mg/l for ibuprofen and 5.020.0 g/l for naproxen. The minimal sample pretreatment and relatively low running costmake isotachophoresis a good alternative to existing methods. 2001 Elsevier Science B.V. All rights reserved.

Keywords: Capillary isotachophoresis; Fluorescence spectrometry; Ibuprofen; Naproxen

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1. Introduction

Ibuprofen, [(R,S)--methyl-4-(2-methylpropyl)-benzeneacetic acid], is a non-steroidal anti-inflammatory drug (NSAID) used in the treat-ment of pain and inflammation in rheumatic dis-ease and other musculoskeletal disorders [1].Naproxen, [(S)-6-methoxy--methyl-2-naphthale-neacetic acid], is another member of this group ofNSAIDs. It is widely used in the treatment ofosteo- and rheumatoid arthritis and for the relief

of mild to moderate pain [2]. A variety of meth-ods are available in the literature for the determi-nation of these compounds in pure form orpharmaceutical formulations including potentio-metric titration [3], flow-injection analysis-FT-IR[4], high-performance liquid chromatography[5,6], supercritical fluid chromatography [7] foribuprofen and spectrofluorimetry [8] fornaproxen. Until now, liquid chromatography hasbeen the major technique used for the determina-tion of ibuprofen and naproxen in tablets. Thesame technique was also applied to collect thedata in the United States Pharmacopoeia mono-graph on ibuprofen [9] and naproxen [10]. Re-

* Corresponding author.E-mail address: [email protected] (J. Polonsky).

0731-7085/01/$ - see front matter 2001 Elsevier Science B.V. All rights reserved.

PII: S0731-7085(01)00374-0

J. Sadecka et al. / J. Pharm. Biomed. Anal. 25 (2001) 881891882

cently, capillary electrophoresis (CE) has gainedin interest, with growing attention to NSAIDsanalysis in general [1113]; conditions for thedetermination of ibuprofen [1416] and naproxen[14,17,18] in a tablet dosage form have been de-scribed. CE offers an alternative technique; how-ever, there is a general lack of acceptance of CEas a routine analytical tool, particularly in theregulatory environment. The high resolutionwhich may be attained with CE has been shownto be especially useful for stereoselective determi-nation of S-naproxen in tablets [18]. In addition,micellar electrokinetic capillary chromatographyoffers a fast separation with complete resolutionbetween ibuprofen, codeine and their nine poten-tial degradation products and excipients [16].

In our country recommended methods foribuprofen and naproxen are European Pharmaco-poeia methods. In European Pharmacopoeia thetitrimetric methods with sodium hydroxide inmethanol using phenolphthalein as chemical indi-cator are described for the routine determinationof ibuprofen [19] and naproxen [20] in pure form.The utilization of chemical indicators for the indi-cation of the end-point of the titration in thepresence of coloring or insoluble excipients intablets is fairly problematic.

The aim of the present contribution was todevelop a isotachophoretic method for the deter-mination of ibuprofen and naproxen in tabletdosage form as an alternative to the above-men-tioned methods. The isotachophoresis is a simple,quick and low-cost method and therefore wellsuited for main drug determination. We havecompared this method with fluorescencespectrometry.

2. Experimental

2.1. Instrumentation

2.1.1. ITPA ZKI 02 isotachophoretic analyzer (Villa

Labeco, Slovak Republic) equipped with a con-ductivity detector and a separation capillary(900.8 mm i.d.) was used. The driving currentwas 250 A.

Hydrochloric acid (10 mmol/l) adjusted withcreatinine to pH 5.0 plus 0.1%polyvinylpyrrolidone was used as the leading elec-trolyte (LE) and 10 mmol/l 4-morpholineethane-sulfonic acid as the terminating electrolyte (TE).

2.1.2. Fluorescence spectrometryAll fluorescence measurements were done on a

Perkin-Elmer LS 50 Luminescence spectrometerequipped with a xenon discharge lamp (20 kW)and 11 cm quartz cell. The LS 50 spectrometerwas interfaced with an Epson PC AX2 microcom-puter supplied with FL Data Manager Software(Perkin-Elmer) for spectral acquisition and subse-quent manipulation of spectra. Experimentalparameters for ibuprofen were: EX=224 nm,EM=290 nm and slit with 3.0 nm. Experimentalparameters for naproxen were: EX=230 nm,EM=355 nm and slit with 3.0 nm.

2.2. Chemicals and samples

Hydrochloric acid, sodium hydroxide andpolyvinylpyrrolidone (PVPD) were obtained fromLachema, creatinine and 4-morpholineethanesul-fonic acid (MES) from Merck. Ibuprofen andnaproxen were obtained from Sigma.

Stock solutions (800 mg/l) were prepared bydissolving 200.0 mg of the active compounds with50 ml of 0.02 mol/l NaOH, and then diluting withdistilled water into a 250.0-ml volumetric flask.These solutions were finally diluted either withwater before the ITP measurements or with 0.05mol/l NaOH before the fluorescence measure-ments. Ibuprofen and naproxen do not show al-ternations when using water and/or alkalinesolutions as a solvent [21]. According to Herce-gova et al. [22], ibuprofen and naproxen are stablein the leading electrolyte solutions used.

The Ibuprofen was labeled as containing 200mg or 400 mg ibuprofen, corn starch, stearin,colloidal silicon dioxide, carboxymethyl starch-sodium salt, hydroxypropylmethylcellulose, tita-nium dioxide, erythrosin and silicone emulsion.

The Naprosyn was labeled as containing 250mg naproxen, lactose and yellow pigment E 102(i.e. tartrazine).

J. Sadecka et al. / J. Pharm. Biomed. Anal. 25 (2001) 881891 883

2.3. Calibration cure

Solutions for the ITP calibration curve wereprepared by appropriate dilution of the stocksolution with water. The concentration range was40.0200.0 mg/l; five standard solutions were pre-pared. Thirty microliters was injected into the ITPcapillary.

Solutions for the fluorescence calibration curvewere prepared by appropriate dilution of thestock solution with NaOH 0.05 mol/l. The con-centration range was 0.46.4 mg/l for ibuprofenand 5.030.0 g/l for naproxen. For each concen-tration range seven standard solutions wereprepared.

2.4. Sample preparation

2.4.1. ITPIn all cases it was assumed that the actual

content of the tablet corresponds to that reportedby the manufacturing laboratories.

Five tablets were weighed and ground. Anamount of the powder, equivalent to one averagedragee, was transferred to a 250.0-ml volumetricflask, mixed with a 50 ml of 0.02 mol/l NaOH andthen made with water up to 250.0 ml volume. Thesample was centrifuged for 1 min at 3000g andappropriate dilutions were made with water to afinal concentration of 80 mg/l. Then 30 l wasinjected into the ITP capillary.

2.4.2. Fluorescence spectrometryFive tablets were weighed and ground. An

amount of the powder, equivalent to one averagedragee, was transferred to a 250.0-ml volumetricflask, mixed with a 50 ml of 0.02 mol/l NaOH andthen made with water up to 250.0 ml volume. Thesample was centrifuged for 1 min at 3000g andappropriate dilutions were made with NaOH 0.05mol/l to a final concentration of 1.6 mg/l foribuprofen and 12.5 g/l for naproxen.

2.5. Stress decomposition studies

Two 10.0-mg amounts of ibuprofen (naproxen)were transferred to two 250-ml flasks. Then, 100.0ml of 1 mol/l NaOH were added to one of the

flasks and 100.0 ml of 0.1 mol/l hydrochloric acidwere added to the other. The two solutions wereboiled under reflux for 36 h. The samples werecollected at 24 h and 36 h. These solutions werethen diluted either with 0.05 mol/l NaOH beforethe fluorescence measurements or with water be-fore the ITP measurements. For the ITP, thesolutions were finally neutralized with NaOH orwith MES to pH 5. Thirty microliters of eachsolution was injected into the ITP system.

3. Results and discussion

3.1. ITP

The physicochemical properties of analytes, es-pecially their low solubility in water and lowmobility complicated the choice of a suitable elec-trolyte system. The isotachophoretic experimentsshowed that the pH of the leading electrolytemust be between 4.5 and 5.5 to ensure sufficientdissociation and effective mobility of the analytes[22]. The effect of pH was studied from 4.5 to 5.5with 6-aminocaproic acid and from 5.0 to 5.5 withcreatinine. In the pH range studied, the carboxylicgroup of analytes is dissociated and thus theanalytes migrate as the anion. In the pH range4.55.5, MES as one of the slowest anionic termi-nators works well and ensures a correct ITP mi-gration. In more acidic electrolyte systems(pH4.5) there is a lack of suitable slow migrat-ing terminators. At pH5.5 all analytes migratein the terminator. Of several electrolyte tested, 10mM creatinine hydrochloride-creatinine buffer(pH 5.0) and 10 mM MES solution were found tobe the preferred leading and terminating elec-trolytes, respectively. The driving current appliedto the capillary was 250 A. The use of a higherdriving current would be rather problematic be-cause even the short capillary caused a highvoltage value when run with MES as the termi-nating electrolyte in the system with a pH of 5.0.In Fig. 1 examples are given of the results of ITPexperiments on (a) a standard solution of ibupro-fen; (b) a sample solution prepared from theIbuprofen tablet; (c) a standard solution ofnaproxen; and (d) a sample solution prepared


Fig. 1. Isotachopherogram of (a) a standard solution of ibuprofen; (b) a sample solution prepared from the Ibuprofen tablet; (c) astandard solution of naproxen; and (d) a sample solution prepared from the Naprosyn tablet. In all cases, the concentration was 80mg/l. Leading electrolyte: hydrochloric acid (10 mmol/l) adjusted with creatinine to pH 5.0 plus 0.1% polyvinylpyrrolidone;terminating electrolyte: 10 mmol/l 4-morpholineethanesulfonic acid. L, leading ion; T, terminating ion; R, increasing resistance.


from the Naprosyn tablet. For the Ibuprofentablet ITP shows only the ibuprofen zone. For theNaprosyn tablet ITP shows only the naproxenzone. No interference from the sample solventand dosage form excipients could be observed.The fact that the excipients in the above-men-tioned tablets do not include acidic substancesprovides evidence that the excipients do not effectthe isotachopherograms. The potential impuritiesin ibuprofen are: 2-(4-methylphenyl)propionicacid (I); 2-(4-butylphenyl)propionic acid (II);2-(4-isobutylphenyl)propionamide (III); 2-(3-iso-butylphenyl)propionic acid (IV); and 4-isobuty-lacetophenone (V) [19]. These compounds werenot, however, readily commercially available.Compared with ibuprofen, the first compound (I)has higher effective mobility, while compounds IIIand V are not acidic compounds. Hence, it isunlikely that interference with ibuprofen wouldoccur in a system such as that described here.Compounds II and IV probably may interferewith the determination of parent drug as similarmobilities to that of ibuprofen could be expected.According to European Pharmacopoeia [20], nonaproxen impurities were considered.

In Table 1 the average values and relative stan-dard deviations are given for the relative stepheights (RSHs) measured with the conductivitydetector. Linearity was observed from 40.0 to200.0 mg/l of ibuprofen (naproxen), with a coeffi-

cient of determination (r2) of 0.999. The equationfor the calibration curve is: y=a+bx, where y isthe zone length (s) and x is the concentration(mg/l). Calibration data are given in Table 1. Forthe limit of quantitation (LOQ), the value (y+10S)/b was used, whereby the calculated interceptof the calibration line can be used as an estimateof y, S is the standard deviation in the y-directionof the calibration line and b is the slope of thecalibration line. For the limit of detection (LOD),the value (y+3S)/b was calculated.

The accuracy and precision of the method wereevaluated by analyzing five replicates of spikedsamples at each of three concentrations (80.0,120.0 and 200.0 mg/l) against a calibration curve.The accuracy was given by the percent error[(mean of measuredmean of added)/mean ofadded]100. Precision was evaluated as the rela-tive standard deviation (R.S.D.). The ITP methodprovides satisfactory precision and accuracy forthe analysis of ibuprofen and naproxen (Table 2).The R.S.D. values were found to be between 0.6and 1.0% for ibuprofen and 0.5 and 1.2% fornaproxen. The accuracy was found to be between0.7 and 2.9% for ibuprofen and 1.4 and+1.6% for naproxen.

Although all samples in the current study weregenerally analyzed within 6 h after dissolution, theresults of sample stability studies demonstratedthat the samples could be stored at 4C for at

Table 1ITP and fluorescence results for RSH reproducibility and calibration

Parameter ITP Fluorescence spectrometry

Ibuprofen Naproxen Ibuprofen Naproxena

0.47RSH 0.440.80.9 R.S.D. (%) (n=5)

40.0200.0 40.0200.0Range (mg/l) 0.42.4 5.020.00.03 0.09Intercept (a) 4.4 1.20.08 0.12Sab 7.5 3.2

148.0 11.7Slope (b) 0.116 0.1095.2 0.2Sbb 0.002 0.002

0.99920.99890.9995r2c 0.99952/7 4/12 0.2/0.5 0.9/3LOD/LOQ (mg/l)

a Range (g/l).b Standard deviation values of intercept (Sa) and slope (Sb).c Coefficient of determination.


Table 2Determination of ibuprofen and naproxen in synthetic samples

Compound ITPa Fluorescence spectrometryb

FoundAdded Accuracy R.S.D. Added Found Accuracy R.S.D.(mg/l) (%) (%) (mg/l)c (mg/l)c (%)(mg/l) (%)

Ibuprofen80.0 79.4 0.7 0.8 0.80 0.85 +6.2 1.2

119.1 0.7 1.0 1.20120.0 1.18 1.7 1.2194.2 2.9 0.6 2.40 2.32 +3.3200.0 1.6

Naproxen81.3 +1.6 0.5 5.080.0 4.6 7.6 2.0

118.3 1.4 0.8 10.0 9.9 0.5 1.8120.0199.8 0.1 1.2 20.0 19.4 3.0 1.6200.0

a Based on five replicate analyses.b Based on three replicate analyses.c Concentrations in g/l for naproxen.

least 5 days without significant degradation.Stored samples were re-analyzed after 5 days andgave acceptable and comparable data to freshlyprepared samples. Assay figures were within 3%agreement for stored and freshly prepared sam-ples and no degradation zones were observed inthe analysis of the stored sample solutions. Thus,a sample solution shelf-life of 5 days was assigned.A longer shelf-life was not required in this studyand therefore a more extensive shelf-life determi-nation was not performed.

For the ruggedness study, preparation of LEand influence of changes of capillaries and instru-ments were investigated in terms of RSH repro-ducibility. The ruggedness results are reported inTable 3. As seen in Table 3, LE to LE andinstrument to instrument RSH reproducibilityfalls within the range of normal precision as pre-sented earlier (Table 1). Capillary to capillaryreproducibility is somewhat higher.

3.2. Fluorescence spectrometry

Ibuprofen emits maximum fluorescence at 290nm when excited at 224 nm (Fig. 2). The spectralcharacteristics are almost independent of the solu-tion pH. No significant changes of the fluores-cence intensity as a function of pH were observed.Naproxen solutions show a strong fluorescencewhich is not dependent over the pH 114 range

[23]. The excitation and emission spectra ofnaproxen in phosphate buffer (pH 6.8; 0.04 mol/l)and alkaline aqueous solutions (0.05 mol/lNaOH) are shown in Fig. 3. As seen from Fig. 3,naproxen emits maximum fluorescence at 355 nmwhen excited at 230 nm. No attempts were madeto distinguish between ibuprofen and its possibleimpurities.

The calibration dependence was polynomialfrom 0.4 to 6.4 mg/l for ibuprofen and from 5.0 to30.0 g/l for naproxen. The calibration plot wasfound to be linear in the range 0.42.4 mg/l foribuprofen and 5.020.0 g/l for naproxen. Theequation for the calibration curve is: y=a+bx,where y is the relative fluorescence intensity and xis the concentration of ibuprofen (mg/l) andnaproxen (g/l), respectively. Calibration data aregiven in Table 1.

Table 3Reproducibility of ITP method ruggedness

IbuprofenaExperimental Naproxena

parameter% R.S.D., RSHchange % R.S.D., RSH

0.70.8LE to LE0.9Instrument to 0.9

instrumentCapillary to capillary 1.01.1

a Sample: 50 g/ml. Values are the results of five replicatemeasurements.


Fig. 2. Fluorescence excitation (a,b) and emission (a, b)spectra of ibuprofen in phosphate buffer (pH 6.8; 0.04 mol/l)(a,a) and 0.05 mol/l NaOH (b,b). In all cases, the concentra-tion was 4 mg/l. For recording emission spectra EX, 224 nm;for excitation, EM, 290 nm.

Table 4Reproducibility of fluorescence method ruggedness

NaproxenbIbuprofenaExperiment parameterchange % R.S.D., RFIc % R.S.D., RFIc

1.4 0.8NaOH to NaOHNaOH to phosphate 4.75.6

buffer

a Sample: 4 mg/l. Values are the results of five replicatemeasurements.

b Sample: 20 g/l. Values are the results of five replicatemeasurements.

c RFI, relative fluorescence intensity.

ported in Table 4. As seen in Table 4, NaOH toNaOH relative fluorescence intensity reproduci-bility falls within the range of normal precisionas presented earlier. NaOH to phosphate bufferrelative fluorescence intensity reproducibility issomewhat higher.

3.3. Stress decomposition studies

To evaluate of the capacity of the ITPmethod for indicating stability, ibuprofen(naproxen) solutions in NaOH (1 mol/l) and hy-drochloric acid (0.1 mol/l) were boiled underreflux for 36 h and analyzed. In the alkalinemedium, ibuprofen and naproxen were foundundegraded after 36 h, while only 83% (66%) ofibuprofen and 73% (62%) of naproxen werefound in the acidic solutions after 24 h (36 h).In both cases, one degradation product ap-peared just before the primary ibuprofen(naproxen) zone. A high concentration of thisproduct may interfere with determination of theparent drug. If necessary, better separation canbe accomplished by reducing the pH of the LEto 4.54.0. When naproxen is subjected toacidic hydrolysis by strong acid, it is hydrolyzedto 6-O-desmethylnaproxen [23]. As we haveshown earlier, naproxen and 6-O-desmethyl-naproxen could be well separated when the lead-ing electrolyte consisted of 10 mol/l hydrochloricacid, -alanine, pH 4.0 and 0.1% methylhydrox-ypropylcellulose [24]. This LE also allowed abetter separation of ibuprofen and its degrada-

Data for the variation of the precision andaccuracy given in Table 2 indicate a R.S.D.from 1.2 to 1.6% and accuracy from 1.7 to6.2% for ibuprofen and R.S.D. from 1.6 to 2.0%and accuracy from 0.5 to 7.6% fornaproxen.

For the ruggedness study, NaOH (0.05 mol/l)preparation to NaOH (0.05 mol/l), and NaOH(0.05 mol/l) to phosphate buffer (0.04 mol/l, pH6.8), relative fluorescence intensity reproducibil-ity was measured. The ruggedness results are re-

Fig. 3. Fluorescence excitation (a,b) and emission (a, b)spectra of naproxen in phosphate buffer (pH 6.8; 0.04 mol/l)(a,a) and 0.05 mol/l NaOH (b,b). In all cases, the concentra-tion was 20 g/l. For recording emission spectra EX, 230 nm;for excitation, EM, 355 nm.


Fig. 4. Isotachopherogram of (a) ibuprofen and (b) naproxen in 0.1 mol/l hydrochloric acid subjected to thermal decomposition for36 h. Leading electrolyte: hydrochloric acid (10 mmol/l) adjusted with -alanine to pH 4.0, plus 0.1% methylhydroxypropylcellulose;terminating electrolyte: 10 mmol/l 4-morpholineethanesulfonic acid. Driving current was 250 A. L, leading ion; T, terminating ion;R, increasing resistance; Dnp, 6-O-desmethylnaproxen.

tion product. Fig. 4 shows the isotachophero-grams of ibuprofen and naproxen in 0.1 mol/lhydrochloric acid subjected to thermal decompo-sition for 36 h. The fluorescence method showscomparable values for the undegraded amounts ofibuprofen and naproxen. In the alkaline medium,ibuprofen and naproxen were found undegradedafter 36 h, while only 79% (65%) of ibuprofen and75% (63%) of naproxen were left in the acidicsolutions after 24 h (36 h). In the case of ibupro-fen, no degradation product appeared in the emis-sion spectra (Fig. 5). For naproxen in acidicmedium, the emission bands of naproxen (EM=355 nm) and 6-O-desmethylnaproxen (EM=420nm) were quite satisfactory resolved so as to beuseful for the direct simultaneous determinationof both compounds (Fig. 6). However, spectraloverlaps may occur in their binary mixtures whenone compound is present in large excess. Forseparating binary mixtures of naproxen and 6-O-desmethylnaproxen the synchronous scanning ap-proach was used [23,24].

3.4. Determination of ibuprofen and naproxen

The ITP and fluorescence methods were thenapplied for the determination of ibuprofen andnaproxen in tablets; the results are given in Table5. As can be seen, the two techniques seem to be

Fig. 5. Fluorescence emission spectra of ibuprofen in 1 mol/lNaOH (a) and 0.1 mol/l hydrochloric acid (b) subjected tothermal decomposition for 36 h. EX, 224 nm.


Fig. 6. Fluorescence emission spectra of naproxen in 1 mol/lNaOH (a) and 0.1 mol/l hydrochloric acid (b) subjected tothermal decomposition for 36 h. EX, 230 nm.

results in terms of repeatability values ofnaproxen. The influence of the matrix can beresponsible of the poor repeatability values ob-tained with fluorescence spectrometry.

To compare the performances of HPLC, CEand ITP, the within-day precision for correctedmigration time, RSH, peak area and zone lengthwere considered and the calibration graphs ob-tained using the different methods were compared(Table 6). In the analyses with HPLC, CE andITP for both components, a linear relationshipbetween measured peak area or zone length andconcentration of the components is obtained withr2 better than approximately 0.999. Concentrationsensitivity of ITP is comparable with that of CE,although the mass sensitivity of CE is higher thanthat of ITP. The reason is that the injectionvolume in CE lies in the range of several nano-liters while that in ITP is in the range of micro-liters. The concentration sensitivity of CE isgenerally lower than that of HPLC when UVabsorbance detection is employed in both tech-niques. This is due to the to short path lengthimposed by the small diameter in CE. The withinday-precision with the CE method for correctedmigration times was less than 1%; the ITP methodhas the same order of within-day precision of theRSHs. Precision of injection, as measured in peakarea repeatability is generally poorer in CE thanin HPLC, typical values being 12% and 0.51%

suitable to carry out the determination of theibuprofen and naproxen in the usual concentra-tions that they are found in the analyzed samples,that is, considering the original quantities in thetablets. The best LOQ was obtained by usingfluorescence spectrometry. Considering that theobtained LOQ values are in any case muchsmaller than the concentration values expected tobe observed from real samples, it can be con-cluded that the two techniques are suitable tocarry out this type of determination. From thevalues given in Table 5 it can be deduced that ITPand fluorescence spectrometry render similar re-peatability for ibuprofen, while ITP gives better

Table 5Analysis of dosage forms

Label claim ITP Fluorescence spectrometryProduct

(active (mg) Assay result Recovery R.S.D. Assay result Recovery R.S.D.compound) (mg) (%) (%)(%) (mg) (%)

203.0 101.5 1.2 199.3 99.6 2.1Ibuprofen 2001.398.0196.11.8(ibuprofen) 96.2192.4200

196.8 98.4 1.4200 195.8 97.9 1.83.1100.0200.00.9100.8201.7200

100.6201.31.5 1.2101.5203.0200399.9 100.0 1.9 399.4 99.8400 1.8

250 252.0 100.8Naprosyn 2.0 251.2 100.5 4.5(naproxen) 250 252.0 100.8 1.2 254.7 101.9 3.6

3.699.8249.41.3101.6250 254.0250 249.4 99.8 1.3 250.6 100.2 5.5250 248.3 99.9 2.1 245.0 98.0 3.6


Table 6Validation data of the HPLC, CE and ITP methods

NaproxenIbuprofenParameter

HPLC [5] CE [15] ITP HPLC [6]HPLC [6] CE [18]a ITP

0.9% R.S.D., RSHb 0.80.9b,c 0.8Linearity range 060 210 550 40200 060 40120 (1.428) 40200

tested (g/ml)0.9996 0.99950.9994 0.9995r2 0.9994 (0.9957) 0.9995

50 ng/ml 1g/ml 2 g/ml 0.5 ng (210 ng/ml)LOD 4 g/ml0.5 ng0.2 0.8 0.41.3 12 1.220.2% R.S.D., peak 0.71.7 (1.99.0)

(zone length)area (zone length)12.5Run time (min) 711 7 8 9 7UV 215 nm UV 214 nm Conductivity UV 260 nmUV 225 nm UV 210 nmDetection Conductivity

a Data for S-naproxen. Data for R-naproxen are in the brackets.b Corrected migration time for CE.c Data from [17].

R.S.D., respectively. The within-day precisionwith the ITP method for the zone lengths was12%. It can be concluded that the precision ofHPLC experiments is by far the best. The sam-ple preparation method employed for ITP issimilar to that for CE and HPLC. The assaytime by ITP and CE is shorter than that byHPLC. A long preconditioning process is re-quired only for HPLC. Flushing with NaOH so-lution and buffer or LE is sufficient in CE andITP. ITP offers same advantages over conven-tional chromatographic methods: (i) non-ioniccompounds, which are frequently components ofthe tablets, do not interfere with the analysis ofthe ionic compounds; (ii) low running cost (twoorder of magnitude compared with HPLC), de-creased cost of capillaries; and (iii) no organicsolvents are used in the preparation of LE. Thelargest drawback of ITP is lower resolution ascompared with CE.

References

[1] S.S. Adams, P. Bresloff, C.G. Mason, J. Pharm. Phar-macol. 28 (1976) 256257.

[2] C.S. Boynton, C.F. Dick, G.H. Mayor, J. Clin. Phar-macol. 28 (1988) 512517.

[3] O. Cakirer, E. Kilic, O. Atakol, A. Kenar, J. Pharm.Biomed. Anal. 20 (1999) 1926.

[4] S. Garrigues, M. Gallignani, M. Delaguardia, Talanta40 (1993) 8993.

[5] S. Ravisankar, M. Vasudevan, M. Gandhimathi, B.Suresh, Talanta 46 (1998) 15771581.

[6] B.M. Lampert, J.T. Stewart, J. Chromatogr. 504 (1990)381389.

[7] N.K. Jagota, J.T. Stewart, J. Chromatogr. 604 (1992)255260.

[8] A. Navalon, R. Blanc, M. del Olmo, J.L. Vilchez, Ta-lanta 48 (1999) 469475.

[9] The United States Pharmacopoeia, XXIII, 1995, pp.785786.

[10] The United States Pharmacopoeia, XXIII, 1995, pp.10531055.

[11] J.R. Veraart, C. Gooijer, H. Lingeman, N.H. Velthorst,U.A. Th. Brinkman, J. Chromatogr. B 719 (1998) 199208.

[12] S. Cherkaoui, J.-L. Veuthey, J. Chromatogr. A 874(2000) 121129.

[13] S. Fanali, J. Chromatogr. A 875 (2000) 89122.[14] R. Weinberger, M. Albin, J. Liq. Chromatogr. 14

(1991) 953972.[15] M.G. Donato, W. Baeyens, W. van den Bossche, P.

Sandra, J. Pharm. Biomed. Anal. 12 (1994) 2126.[16] K. Persson-Stubberud, O. Astrom, J. Chromatogr. A

798 (1998) 307314.[17] A. Guttman, N. Cooke, J. Chromatogr. A 685 (1994)

155159.[18] M. Fillet, L. Fotsing, J. Bonnard, J. Crommen, J.

Pharm. Biomed. Anal. 18 (1998) 799805.


[19] European Pharmacopoeia, 1997, pp. 1001-1002.[20] European Pharmacopoeia, 1997, pp. 1219-1220.[21] H.J. Battista, G. Wehinger, R. Henn, J. Chromatogr. 345

(1985) 7789.[22] A. Hercegova, J. Sadecka, J. Polonsky, Electrophoresis 21

(2000) 28422847.[23] D.G. Konstantianos, P.C. Ioannou, E. Stratikos, Anal.

Chim. Acta 290 (1994) 3439.[24] M. E`akrt, A. Hercegova, J. Lesko, J. Polonsky, J.

Sadecka, I. Skae`ani, J. Chromatogr. A (2000) in press.

.

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