Article

Determination of Potential Impurities of Naproxen Sodium in Soft Gelatin Capsules Dosage by Using Ultra Performance Liquid Chromatography

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Abstract

A simple, sensitive and rapid RP-UPLC method was developed and validated for quantification of seven potential impurities of Naproxen sodium in Naproxen sodium soft gelatin capsules. The separation of impurities from drug sample matrix is achieved by Acquity BEH C18 (100 mm × 2.1 mm) 1.7 µ column. The optimized Mobile phase A consists of 0.1 % OPA in water, pH adjusted to 3.0 by using diluted NaoH, for Mobile phase B acetonitrile is used. The Separation of impurities achieved using gradient elution mode at 0.5 mL/min flow rate with working wavelength of 230 nm. The column temperature maintained at 50°C. The Injection volume fixed at 3 µL and run time is about 13 minutes. The developed RP-UPLC method is validated according to the International Conference on Harmonization analytical procedures and methodology Q2(R1) for, linearity, specificity accuracy, LOD, LOQ, precision, robustness, ruggedness and solution stability. Validated method is robust and stability indicating for the determination of all impurities which may arise during shelf life of the drug product. This method is useful in quality control laboratories to generate precise results in faster rate due to its shorter run time.

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... In the next study, RP-UPLC technique was successfully applied for complete separation the seven potential impurities of naproxen sodium in gelatin capsules [11]. Sample solutions were made in different stress conditions i.e., acidic degradation (5M HCl/60 min/25 • C/1 mL), alkaline degradation (5M NaOH/120 min/85 • C/1 mL), peroxide degradation (30% H 2 O 2 /60 min/25 • C/1 mL), thermal (24 h/60 • C), Processes 2020, 8,962 3 of 21 humidity (90% RH/120 h/25 • C) and photolytic (10 K Lux/120 h + UV 200 watt hours/m 2 ). ...
... Numerous analytical methods like spectrophotometry [19,[26][27][28], titration [29], microextraction [30], voltammetry [31][32][33] chromatographic technologies in combination with various detection systems (HPLC, UPLC, GC, TLC) [5][6][7][8][9][10][11][12][13][14]18,20,28,32,[34][35][36][37][38][39][40][41][42][43][44] and also electrophoresis [45,46] were utilized for the naproxen determination in different matrix in sampling biological materials (e.g., urine, plasma), water samples (wastewater), and also in simple and complex drug formulations. ...
... Several, but mostly HPLC and UPLC methods have been reported to examine naproxen and its related compounds (impurities) in pharmaceutical formulations [9][10][11][12][13][14]. ...
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... Reddy et al. [21] reported a simple, rapid, gradient reversephase ultra-performance liquid chromatography (RP-UPLC) method for determination of NAP in the presence of its impurities. Study revealed total seven impurities, which are characterized on the basis of stress degradation studies. ...
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Naproxen sodium (Anaprox) is a potent antiinflammatory and analgesic agent. The drug has demonstrated a variety of biologic actions, including stabilization of lysosomal membranes, but most of its therapeutic activity is probably mediated through prostaglandin synthesis inhibition. The linkage between inhibition of prostaglandin synthesis and relief of dysmenorrhea has been documented in clinical studies, reported elsewhere in this supplement. Of relevance is the selective activity of naproxen sodium on uterine microsomal preparations. Once dissolved in biologic fluids, naproxen and naproxen sodium are chemically identical species and have the same biologic properties. Administration of naproxen as the sodium salt (Anaprox), however, permits more rapid absorption from the gastrointestinal tract. In either form, the drug is essentially completely absorbed. Its metabolic half-life averages 13 hours. The metabolism of naproxen is quite simple: it is excreted almost entirely in the urine as the native molecule, its oxidative 6-desmethyl metabolite and their respective conjugates. Naproxen is an acidic drug that is highly bound to plasma albumin. It may thus be expected to displace and transiently increase the tissue availability of other protein-bound drugs. In practice, however, potential interactions with both warfarin and tolbutamide have been evaluated and do not appear to be of clinical significance. Naproxen has a high therapeutic index and a shallow dose-response curve, so the effect of other drugs on its pharmacokinetics is not likely to have a large clinical impact.
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A simple, selective and sensitive high performance liquid chromatographic (HPLC) method has been developed for the simultaneous determination of naproxen and its main degradation products such as 1-(6-methoxy-2-naphthyl) ethanol (MNE), 2-methoxy-6-ethyl naphthalene (MEN) and 2-acetyl-6-methoxy naphthalene (AMN). The separation of these compounds was achieved on porous graphitic carbon (PGC) column using tetrahydrofuran-methanol as the mobile phase, and the effluent from the column was monitored at 272 nm. At a flow rate of 1 ml min(-1), the retention time of the last eluting compound was less than 10 min. Correlation coefficient for calibration curves in the ranges 2-25 microg ml(-1) for all compounds studied were greater than 0.999. The sensitivity of detection is 0.05 microg l(-1) for naproxen, MNE and MEN and 0.20 microg ml(-1) for AMN. The reproducibility of the peak area of these compounds using isocratic elution were quite high, and the standard deviations (S.D.) were below 2% (n=5). The reproducibility of retention times of these compounds was within 1% (n=5). The proposed liquid chromatographic method was successfully applied to the analysis of commercially available naproxen sodium (NS) dosage forms with recoveries of 98.8-102%. A comparative study shows that the selectivity of these compounds on PGC column was different to that obtained with octadecyl silica (ODS) columns.
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We compared the variability in degree and recovery from steady-state inhibition of cyclooxygenase (COX)-1 and COX-2 ex vivo and in vivo and platelet aggregation by naproxen sodium at 220 versus 440 mg b.i.d. and low-dose aspirin in healthy subjects. Six healthy subjects received consecutively naproxen sodium (220 and 440 mg b.i.d.) and aspirin (100 mg daily) for 6 days, separated by washout periods of 2 weeks. COX-1 and COX-2 inhibition was determined using ex vivo and in vivo indices of enzymatic activity: 1) the measurement of serum thromboxane (TX)B(2) levels and whole-blood lipopolysaccharide-stimulated prostaglandin (PG)E(2) levels, markers of COX-1 in platelets and COX-2 in monocytes, respectively; 2) the measurement of urinary 11-dehydro-TXB(2) and 2,3-dinor-6-keto-PGF(1alpha) levels, markers of systemic TXA(2) biosynthesis (mostly COX-1-derived) and prostacyclin biosynthesis (mostly COX-2-derived), respectively. Arachidonic acid (AA)-induced platelet aggregation was also studied. The maximal inhibition of platelet COX-1 (95.9 +/- 5.1 and 99.2 +/- 0.4%) and AA-induced platelet aggregation (92 +/- 3.5 and 93.7 +/- 1.5%) obtained at 2 h after dosing with naproxen sodium at 220 and 440 mg b.i.d., respectively, was indistinguishable from aspirin, but at 12 and 24 h after dosing, we detected marked variability, which was higher with naproxen sodium at 220 mg than at 440 mg b.i.d. Assessment of the ratio of inhibition of urinary 11-dehydro-TXB(2) versus 2,3-dinor-6-keto-PGF(1alpha) showed that the treatments caused a more profound inhibition of TXA(2) than prostacyclin biosynthesis in vivo throughout dosing interval. In conclusion, neither of the two naproxen doses mimed the persistent and complete inhibition of platelet COX-1 activity obtained by aspirin, but marked heterogeneity was mitigated by the higher dose of the drug.
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