- About this Journal ·
- Abstracting and Indexing ·
- Advance Access ·
- Aims and Scope ·
- Article Processing Charges ·
- Articles in Press ·
- Author Guidelines ·
- Bibliographic Information ·
- Citations to this Journal ·
- Contact Information ·
- Editorial Board ·
- Editorial Workflow ·
- Free eTOC Alerts ·
- Publication Ethics ·
- Reviewers Acknowledgment ·
- Submit a Manuscript ·
- Subscription Information ·
- Table of Contents
ISRN Analytical Chemistry
Volume 2012 (2012), Article ID 281929, 13 pages
Fluorometric Determination of Drugs Containing α-Methylene Sulfoxide Functional Groups Using - Methylnicotinamide Chloride as a Fluorogenic Agent
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Tanta University, Tanta 31527, Egypt
Received 10 October 2011; Accepted 13 November 2011
Academic Editors: C. Desiderio and W. Lee
Copyright © 2012 Khaled M. Elokely et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
A simple fluorometric method, using -methylnicotinamide chloride (NMNCl) as a fluorogenic reagent, has been developed, adapted, and validated for the quantitative estimation of drugs containing α-methylene sulfoxide functional groups. The proposed method has been applied successfully to the determination of sulindac (1), omeprazole (2), lansoprazole (3), pantoprazole (4), and rabeprazole (5) in the pure form, laboratory-prepared mixtures, pharmaceutical dosage forms, spiked human plasma samples, and in hospitalized patient's or volunteer's blood. For the standard solutions of 1, 2, 3, 4, and 5, the method showed linearity over concentration ranging between 1–50 g/mL, 50–1200 ng/mL, 100–1500 ng/mL, 10–1500 ng/mL, and 20–2200 ng/mL, respectively. For the spiked human plasma of 1, 2, 3, 4, and 5, the linearity was shown over concentration ranging between 1–50 μg/mL, 75–1200 ng/mL, 100–1400 ng/mL, 10–1500 ng/mL, and 50–2100 ng/mL, respectively. The method showed good accuracy, specificity, and precision in both laboratory-prepared mixtures and spiked human plasma samples. The proposed method is simple, does not need sophisticated instrumentation, suitable for quality control application, bioavailability, and bioequivalency studies. Besides, the sensitivity and detection limits are comparable to sophisticated chromatographic methods.
Nakamura described the application of a fluorometric method of the reaction of -methylnicotinamide chloride (NMNCl) for the analysis of various compounds containing α-methylene carbonyl functional groups . Nakamura also made qualitative tests on the reaction mechanism and identified the cyclized α-adduct fluorophore . This reaction was not tested before for compounds containing α-methylene adjacent to other functional groups.
Encouraged by the successful application of the NMNCl methodology to the determination of similar to α-methylene carbonyl functional group-containing drugs, namely, warfarin , pentoxifylline, propafenone hydrochloride, and acebutolol hydrochloride  and the almost isosteric α-methylene sulfone/sulfonamide group, such as methyl sulfonyl methane (MSM), tinidazole, and rofecoxib , we began to adapt, validate, and extend the applicability of this methodology for the analysis of sterically hindered cyclic ketones such as ketamine hydrochloride, griseofulvin, and levonorgestrel (unpublished results).
In this paper, we report the application of this methodology for determination of α-methylene sulfoxide functional group-containing drugs such as the nonsteroidal anti-inflammatory drug (NSAID) sulindac (1) and the proton pump inhibitors (PPIs) omeprazole (2), lansoprazole (3), pantoprazole (4), and rabeprazole (5).
Several methods have been reported for the analysis of 1 that may include UV spectrophotometry , reversed-phase HPLC as a stability-indicating assay , other HPLC methods [9, 10], enzyme immunoassay , and capillary electrophoresis [12, 13].
Several methods have been developed for determination, chiral separation, stability, or pharmacokinetic studies of 2 in bulk form, pharmaceuticals or biological samples, and these methods may include different spectrophotometric methods via formation of metal chelates , UV-derivative spectrophotometry  and HPLC methods for its determination , separation of enantiomers , for stability studies , or for the study of its pharmacokinetic profile .
Several methods have been reported for the analysis of 3 that may include UV/visible spectrophotometry  and HPLC for its determination , enantiomeric separation , or pharmacokinetic study .
Several methods have been reported for the analysis of 4 that may include kinetic spectrophotometry using 1-fluoro-2,4-dinitrobenzene , UV spectrophotometry , and different HPLC methods for its determination  or for its metabolites .
The objective of this work is to develop, adapt, and validate a simple fluorometric method that can be applied in the determination of α-methylene sulfoxide group-containing drugs, namely, drugs 1–5 in pure form, dosage forms, spiked human plasma samples and in patient’s blood. The proposed method has minimal instrumentation and chemical requirements; nevertheless, its sensitivity and specificity are comparable to other elaborated chromatographic techniques. In addition, it is a versatile method that can find applications on a wide range of pharmaceutical preparations and biological fluids.
Shimadzu RF 5301 PC spectrofluorometer.
2.2.1. Authentic Drugs
Working standards of 1, 2, 3, 4, and 5 were supplied by Sigma Pharmaceutical Industries, Egypt, Amyria Pharmaceutical Industries, Alexandria, Egypt, T3A Pharma, Egypt, Medical Union Pharmaceuticals (MUP), Egypt, and Global Napi Pharmaceuticals (GNP), Egypt, respectively.
Plasma samples were purchased from the Central Blood Bank of Tanta University Hospital.
2.2.2. Other Chemicals
-Methylnicotinamide chloride was purchased from Sigma Chemicals Co. Formic acid, sodium hydroxide, methanol, and all other chemicals were of analytical grade. Water used was doubly distilled.
2.3. Dosage Forms
2.3.1. Sulindac (1)
Rudac tablet (Sigma Pharmaceutical Industries) was labeled to contain 150 and 200 mg, HiDac tablet (Hipharm for Manufactured Pharmaceuticals) labeled to contain 200 mg.
2.3.2. Omeprazole (2)
Gastrazole capsules, 20 mg (Amyria Pharmaceutical Industries), Epirazole capsules, 20 mg (Egyptian International Pharmaceutical Industries Co. (EIPICO)), Omepak capsules, 10 and 20 mg (Sedico Pharmaceutical Co.), Pepzole capsules, 40 mg (Alkan Pharma), Gasec capsules, 20 mg (Mepha), Omez capsules, 10 mg (Pharaonia Pharmaceuticals PharoPharma), Gastrocure capsules, 20 mg (October Pharma), Napizole capsules, 20 mg (Global Napi Pharmaceuticals (GNP)), Ulstop capsules, 20 mg (Pharco Pharmaceuticals), Risek capsules, 20 mg (Julphar), Gastroloc capsules, 40 mg (Sigma), Omepral capsules, 20 mg (Memphis Co. for Pharmaceuticals and Chemical Industry), Trio capsules, 20 mg (Alkan Pharma), and Nexium tablets, 20 mg esomeprazole (Astra Pharmaceuticals).
2.3.3. Lansoprazole (3)
Lansoprazole capsules, 15 mg (Rexcel), Zollipak capsules, 30 mg (Sedico), Peptazole capsules, 30 mg (Saudi Pharmaceutical Industries and Medical Appliances Corporation (Spimaco), Lanzor capsules, 15 and 30 mg (Aventis Pharma), and Lopral capsules, 30 mg (T3A Pharma).
2.3.4. Pantoprazole (4)
Controloc tablets, 40 mg (Byk Gulden Lomberg Chemische Fabrik GmbH), Pantoloc tablets, 20 and 40 mg (Medical Union Pharmaceuticals (MUP)), and Pantazole tablets, 40 mg (Sigma Pharmaceutical Industries).
2.3.5. Rabeprazole (5)
Bepra tablets, 20 mg (GNP) and Pariet tablets, 20 mg (Janssen Cilag).
All these preparations were purchased from the local market of Egypt except for Nexium that was purchased from Saudi Arabia.
2.4. Reagents and Standard Solutions
2.4.1. Stock Standard Solutions of Drugs
Stock standard solutions were prepared in 0.1 N sodium hydroxide for 1, 2, and 4; 50% aqueous methanol for 3 and methanol for 5 to contain 100 mg/mL for 1, 150 μg/mL for 3, 4, and 5, and 250 μg/mL for 5.
2.4.2. Serial Standard Solutions of Drugs
Aliquots of the stock solutions were diluted quantitatively with the same solvent to obtain concentration ranging between 10–500 μg/mL for 1, 0.1–15 μg/mL for 2, 3, and 4, and 0.1–25 μg/mL for 5.
2.4.3. Assay Solutions of Drugs in Synthetic Mixtures
Several synthetic mixtures were prepared for 1, 4, and 5 to contain different proportions of the possible interfering substances that may be present with the drug in its dosage form. Three synthetic mixtures containing 1 were prepared. The first mixture contained 200 mg 1, 230 mg cellulose, 10 mg magnesium stearate, and 60 mg starch. The second mixture contained 200 mg 1, 100 mg lactose, 60 mg starch, 60 mg gelatin, 8 mg magnesium stearate, and 72 mg talc. The third mixture contained 130 mg avicel instead of lactose and gelatin.
Three synthetic mixtures containing 4 along with various additives and inactive ingredients were prepared. The first mixture contained 20 mg 4, 280 mg avicel, 60 mg maize starch, 10 mg magnesium stearate, 10 mg magnesium carbonate, 1 mg quinolone, 1 mg acidisol, 60 mg talc, 1 mg colloidal silicon, 6 mg polyethylene glycol 6000, 50 mg Eudragit L100-55, and 1 mg titanium dioxide. The second mixture contained 20 mg 4, 280 mg lactose, 60 mg starch, 60 mg gelatin, 8 mg magnesium stearate, and 72 mg talc. The third mixture contained 340 mg avicel instead of lactose and gelatin.
Three synthetic mixtures containing 5 were prepared. The first mixture contained 20 mg 5, 300 mg croscarmellose sodium, 72 mg talc, 1 mg sodium hydroxide, 1 mg titanium dioxide, and 8 mg magnesium stearate. The second mixture contained 20 mg 5, 180 mg lactose, 60 mg starch, 60 mg gelatin, 8 mg magnesium stearate, and 72 mg talc. The third mixture contained 240 mg avicel instead of lactose and gelatin.
Each synthetic mixture of 1 and 4 was extracted with 100 mL 0.1 N sodium hydroxide. The synthetic mixture of 5 was extracted with 100 mL methanol. The extracts were filtered, and the first 10 mL of the filtrate were rejected. Aliquots of the filtrate were diluted with the same solvent to obtain serial solutions in the concentration ranges 10–500 μg/mL, 0.1–15 μg/mL, and 0.1–25 μg/mL for 1, 4, and 5, respectively.
2.4.4. Assay Solutions of Drugs in Their Pharmaceutical Preparations
A quantity of the mixed contents of 20 capsules or tablets equivalent to one capsule or tablet of 1–5 were finely powdered and transferred with the aid of several portions of 0.1 N sodium hydroxide solution (for 1, 2, and 4), 50% aqueous methanol (for 3), or methanol (for 5) to a 100 mL volumetric flask, and the volume was completed with the same solvent. The resulting solution was filtered and the first 10 mL of the filtrate was rejected. Aliquots of the filtrate were diluted with the same solvents to obtain 200 μg/mL, 6 μg/mL, 3 μg/mL, 4 μg/mL, and 6 μg/mL solutions of 1–5, respectively.
2.4.5. Assay Solutions of Drugs in Spiked Human Plasma Samples
Serial Standard Solutions of the Drugs
Serial standard solutions for 1, 2, 3, and 4 were prepared in 0.1 N sodium hydroxide solution in concentrations ranging between 1–50 mg/mL for 1 and 50–1500 μg/mL for 2, 3, and 4. Serial standard solutions of 5 were prepared in methanol in concentrations ranges of 1–2500 μg/mL.
Preparation of Spiked Human Plasma Samples
Two hundred μL of each 1, 2, 3, and 4 serial standard solution were diluted with 1800 μL human plasma and vortex mixed to obtain concentrations ranging between 0.1–5 mg/mL for 1 and 5–150 μg/mL for 2, 3, and 4. For 5 200 μL of each serial standard solution were evaporated, the residue was dissolved in 1800 μL human plasma and vortex mixed, and 200 μL distilled water were added and vortex mixed to obtain 1–250 μg/mL.
Preparation of Assay Solutions of Drugs in Plasma Samples
Two hundred μL of each spiked human plasma samples were mixed with 1800 μL methanol and centrifuged for 15 minutes to separate the precipitated protein. The clear supernatant was filtered through Millipore filter (0.45 μm) to obtain solutions in concentration ranging between 10–500 μg/mL for 1, 0.5–15 μg/mL for 2, 3, and 4, and 0.1–25 μg/mL for 5.
Determination of 1–5 in Volunteer’s Blood or Hospitalized Patient’s Blood
A blood sample was withdrawn in a test tube to which heparin was previously added and dried. The sample was centrifuged to separate plasma and then treated as previously mentioned under preparation of assay solutions of each drug in plasma samples.
2.4.6. N1-Methylnicotinamide Chloride Reagent (NMNCl)
One mM solution of NMNCl reagent was prepared by dissolving 1.7262 g NMNCl in one liter of distilled water. Aliquot of this solution was diluted with distilled water to obtain , , , and mM solutions.
2.4.7. Sodium Hydroxide Reagent
Sodium hydroxide solutions were prepared in distilled water to have concentration of 0.1 N, 1 N, 2 N, 5 N, and 6 N solutions.
2.5. General Fluorometric Procedure
One milliliter of each drug standard solution, assay solution of synthetic mixture, assay solution of pharmaceutical preparation, assay solution of plasma sample, or the assay solution of the volunteer’s plasma was transferred to 10 mL screw capped test tube. Solutions of sodium hydroxide and NMNCl were added. The mixture was cooled in ice for the indicated time then the pH adjusted using formic acid and heated for the indicated time and then was cooled in ice for 5 minutes (optimum NaOH concentration and volume, volume and concentration of added NMNCl, reaction pH values and cooling, and heating times are shown in Table 1). The mixture was transferred to 10 mL volumetric flask and the resulting solution was completed using distilled water. The intensity of the resulting fluorescence was measured at the optimal wavelengths indicated in Table 1.
The fluorometric measurements were performed against reagent blank experiments. Concentrations of the drugs were calculated from the corresponding calibration graphs prepared simultaneously.
3. Results and Discussion
The reaction of NMNCl, with drugs containing active methylene sulfoxide groups, was not previously studied and this is the first application of this reaction to compounds containing this functional group. When 1–5 (for chemical structures, cf. Figure 1 and for plausible chemical pathway, cf. ) were allowed to react with NMNCl under the optimal conditions specified for each, strong fluorescent products were produced except for 1 that was found to have a quenching effect on the fluorescence of the reagent blank used at excitation and emission wavelengths of 285 nm and 315 nm, respectively; compare Figure 2. The optimal wavelengths of excitation and emission of the reaction product were determined using synchronous wavelength search compare Table 1.
Different variables affecting the reaction between the estimated drug and NMNCl, including sodium hydroxide concentration and volume, added NMNCl concentration and volume, cooling time, heating time, and pH variations, were studied to optimize the reaction conditions to give maximum fluorescence intensity; compare Figures 3, 4, 5, 6, 7, 8, and 9.
After optimization of the different reaction parameters, linear relationships between fluorescence intensity and each drug concentration were obtained over the following concentration ranging between 50–1200 ng/mL, 100–1500 ng/mL, 100–1500 ng/mL, and 20–2200 ng/mL in the standard solutions of 2, 3, 4, and 5, respectively, and 75–1200 ng/mL, 100–1500 ng/mL, 100–1400 ng/mL and, 50–2100 ng/mL in plasma samples for 2, 3, 4, and 5, respectively. The linearity range was 1–50 μg/mL in both standard solutions and spiked human plasma samples for the observed fluorescence quenching produced by 1.
These results reveal a good and dynamic linearity ranges of the proposed method with different drugs. The good linearity of these relations was indicated by the corresponding regression equations shown in Tables 2 and 3, for standard solutions and spiked human plasma samples, respectively.
3.1. Detection Limit (DL)
Detection limits were practically determined according to the ICH topic Q2B (R1)  and found to be 0.5 μg/mL, 10 ng/mL, 20 ng/mL, 20 ng/mL, and 1 ng/mL in standard solutions for 1, 2, 3, 4, and 5, respectively, and 0.5 μg/mL, 25 ng/mL, 30 ng/mL, 50 ng/mL, and 10 ng/mL in plasma samples for 1, 2, 3, 4, and 5, respectively.
3.2. Quantitation Limit (QL)
Quantitation limits were practically determined according to the ICH topic Q2B (R1)  and found to be 1 μg/mL, 50 ng/mL, 100 ng/mL, 100 ng/mL, and 20 ng/mL in standard solutions for 1, 2, 3, 4, and 5, respectively, and 1 μg/mL, 75 ng/mL, 100 ng/mL, 100 ng/mL and 50 ng/mL in plasma samples for 1, 2, 3, 4 and 5, respectively. These results show the high sensitivity of the proposed method.
The accuracy of the proposed method was studied according to the ICH topic Q2B (R1) , by preparing standard solutions and spiked human plasma samples containing various concentrations, lying within the linearity range of each drug, and analyzing them using the proposed method. The results, expressed as % recovery ± S.D., are shown in Tables 4 and 5 for standard solutions and spiked human plasma samples, respectively.
The precision of the method was judged by performing intraday and interday triplicate analyses of different concentrations covering the linearity range of each drug in both standard solutions and spiked human plasma samples. The results are reported as S.D. and C.V. in Tables 6 and 7 for standard solutions and spiked human plasma samples, respectively.
To study the method specificity, three synthetic mixtures of 1, 4, and 5 were prepared to contain the possible interfering substances used during pharmaceutical formulations. These mixtures were analyzed using the proposed method and the results, expressed as % recovery ± S.D. No synthetic mixtures were prepared for 2 or 3 because these drugs are supplied as capsules containing the active ingredient without additives. The prepared mixtures were determined by the proposed method and the results, expressed as % recovery ± S.D., were found to be , , and , for 1, 4, and 5, respectively.
3.6. Assay of Pharmaceutical Preparations
All the pharmaceutical preparations available in the local market for each drug were analyzed using the proposed method. The results, expressed as % recovery ± S.D., are illustrated in Table 8.
3.7. Determination of 1–5 in Hospitalized Patient’s or Volunteer’s Blood
The success in the application of the highly sensitive proposed procedure for the determination of 1–5 in spiked human plasma samples with good accuracy and precision encouraged the investigators to study its application for monitoring the drug level in the blood of a volunteer or a hospitalized patient under 1–5 therapy.
The level of 2 was monitored in the blood of a hospitalized patient receiving it with other medications as paracetamol, bromohexine HCl, acephylline piperazine, hyosine N-butylbromide, and captopril. The concentration of 2 in the patient’s blood was found to be 0.31 μg/mL.
The level of each of 1, 3, 4, and 5 was monitored in the blood of volunteers. The concentrations of 1, 3, 4, and 5 in volunteers’ blood were found to be 5.2 μg/mL, 1.1 μg/mL, 3.6 μg/mL, and 0.3 μg/mL, respectively.
The proposed method makes use of the high sensitivity and specificity of the fluorometric analysis to reach low limits of detection and quantitation for all the studied drugs in standard solutions, synthetic mixtures, pharmaceutical preparations, spiked human plasma samples, and patient’s or volunteer’s blood. The method is simple; it gives results comparable to those obtained by other techniques that require elaborate instrumentations and time-consuming sample preparation procedure.
The method showed good accuracy and precision suitable for quality assurance and could be recommended for bioequivalency and bioavailability studies as well as for validation of cleaning methodology prior to line clearance.
The proposed method application could be extended to cover all available pharmaceutical preparations for each of the chosen drugs.
This work was supported by Tanta University, Tanta, Egypt. The authors declare that they do not have any direct contact, work or financial relation with the commercial companies mentioned in their paper.
- H. Nakamura and Z. Tamura, “Fluorometric assay of α-methylene carbonyl compounds with -methylnicotinamide chloride,” Analytical Chemistry, vol. 50, no. 14, pp. 2047–2051, 1978.
- M. A. El Dawy, M. M. Mabrouk, and R. A. El Barbary, “Spectrofluorimetric determination of warfarin sodium by using -methylnicotinamide chloride as a fluorigenic agent,” Journal of Association of Official Analytical Chemists International, vol. 88, no. 2, pp. 455–461, 2005.
- M. A. El Dawy, M. M. Mabrouk, and R. A. El Barbary, “Spectrofluorimetric determination of drugs containing active methylene group using -methylnicotinamide chloride as a fluorigenic agent,” Chemical and Pharmaceutical Bulletin, vol. 54, no. 7, pp. 1026–1029, 2006.
- K. M. Elokely, M. A. Eldawy, M. A. Elkersh, and T. F. El-Moselhy, “Fluorescence spectrometric determination of drugs containing α-methylene sulfone/sulfonamide functional groups using -methylnicotinamide chloride as a fluorogenic agent,” International Journal of Analytical chemistry, vol. 2011, Article ID 840178, 9 pages, 2011.
- R. W. Li, S. W. Seto, A. L. Au et al., “Inhibitory effect of nonsteroidal anti-inflammatory drugs on adenosine transport in vascular smooth muscle cells,” European Journal of Pharmacology, vol. 612, no. 1–3, pp. 15–20, 2009.
- X. Q. Li, T. B. Andersson, M. Ahlström, and L. Weidolf, “Comparison of inhibitory effects of the proton pump-inhibiting drugs omeprazole, esomeprazole, lansoprazole, pantoprazole, and rabeprazole on human cytochrome P450 activities,” Drug Metabolism and Disposition, vol. 32, no. 8, pp. 821–827, 2004.
- K. Y. Jiang, “Blood gas studies in experimental steam burns of the respiratory tract 1 to 14 days after the injuries,” Zhonghua zheng xing shao shang wai ke za zhi = Zhonghua zheng xing shao shang waikf [i.e. waike] zazhi = Chinese journal of plastic surgery and burns / [Chung-hua cheng hsing shao shang wai k"o tsa chih pien chi wei yuan hui pien ch, vol. 1, no. 3, pp. 190–239, 1985.
- D. M. Boland, M. F. Burke, T. Mitchel, and P. Madley, “Development of a generic method to the solid-phase extraction of acidic compounds from complex matrices,” Journal of Analytical Toxicology, vol. 25, no. 7, pp. 602–606, 2001.
- L. X. Jiang, “Rapid analysis of sulindac in human serum by HPLC,” Yaowu Fenxi Zazhi, vol. 20, pp. 163–165, 2000.
- A. Slovakova, X. F. von Maltzan, B. K. Patel, A. F. Drake, and A. J. Hutt, “Chromatographic resolution, chiroptical characterization and urinary excretion of the enantiomers of sulindac,” Chromatographia, vol. 48, no. 5-6, pp. 369–376, 1998.
- B. Unterhalt, S. Baudner, and A. Malcher, “Enzyme immunoassay for the determination of sulindac,” Pharmazie, vol. 53, no. 6, pp. 420–421, 1998.
- P. Zhang, G. Xu, J. Xiong et al., “Enhancing the sensitivity of capillary electrophoresis using a microcolumn solid phase extraction setup,” Journal of Separation Science, vol. 26, no. 17, pp. 1527–1532, 2003.
- Y. L. Chen, Y. J. Jong, and S. M. Wu, “Capillary electrophoresis combining field-amplified sample stacking and electroosmotic flow suppressant for analysis of sulindac and its two metabolites in plasma,” Journal of Chromatography A, vol. 1119, no. 1-2, pp. 176–182, 2006.
- F. Salama, N. El-Abasawy, S. A. Abdel Razeq, M. M. F. Ismail, and M. M. Fouad, “Validation of the spectrophotometric determination of omeprazole and pantoprazole sodium via their metal chelates,” Journal of Pharmaceutical and Biomedical Analysis, vol. 33, no. 3, pp. 411–421, 2003.
- K. Karljikovic-Rajic, D. Novovic, V. Marinkovic, and D. Agbaba, “First-order UV-derivative spectrophotometry in the analysis of omeprazole and pantoprazole sodium salt and corresponding impurities,” Journal of Pharmaceutical and Biomedical Analysis, vol. 32, no. 4-5, pp. 1019–1027, 2003.
- R. M. Orlando and P. S. Bonato, “Simple and efficient method for enantioselective determination of omeprazole in human plasma,” Journal of Chromatography B, vol. 795, no. 2, pp. 227–235, 2003.
- Q. B. Cass, V. V. Lima, R. V. Oliveira, N. M. Cassiano, A. L. G. Degani, and J. Pedrazzoli, “Enantiomeric determination of the plasma levels of omeprazole by direct plasma injection using high-performance liquid chromatography with achiral-chiral column-switching,” Journal of Chromatography B, vol. 798, no. 2, pp. 275–281, 2003.
- A. Ekpe and T. Jacobsen, “Effect of various salts on the stability of lansoprazole, omeprazole, and pantoprazole as determined by high-performance liquid chromatography,” Drug Development and Industrial Pharmacy, vol. 25, no. 9, pp. 1057–1065, 1999.
- J. F. Marier, M. C. Dubuc, E. Drouin, F. Alvarez, M. P. Ducharme, and J. L. Brazier, “Pharmacokinetics of omeprazole in healthy adults and in children with gastroesophageal reflux disease,” Therapeutic Drug Monitoring, vol. 26, no. 1, pp. 3–8, 2004.
- A. M. Wahbi, O. Abdel-Razak, A. A. Gazy, H. Mahgoub, and M. S. Moneeb, “Spectrophotometric determination of omeprazole, lansoprazole and pantoprazole in pharmaceutical formulations,” Journal of Pharmaceutical and Biomedical Analysis, vol. 30, no. 4, pp. 1133–1142, 2002.
- N. Rahman, Z. Bano, S. N. H. Azmi, and M. Kashif, “A kinetic spectrophotometric method for the determination of lansoprazole in pharmaceutical formulations,” Journal of the Serbian Chemical Society, vol. 71, no. 10, pp. 1107–1120, 2006.
- M. Miura, H. Tada, and T. Suzuki, “Simultaneous determination of lansoprazole enantiomers and their metabolites in plasma by liquid chromatography with solid-phase extraction,” Journal of Chromatography B, vol. 804, no. 2, pp. 389–395, 2004.
- M. L. C. Montanari, Q. B. Cass, A. D. Andricopulo, A. Leitao, and C. A. Montanari, “Identification of chiral selectors for improved enantioseparation based on molecular interaction fields,” Analytica Chimica Acta, vol. 545, no. 1, pp. 33–45, 2005.
- N. Rahman and M. Kashif, “Initial-rate method for the determination of pantoprazole in pharmaceutical formulations using 1-fluoro 2,4-dinitrobenzene,” Pharmazie, vol. 60, no. 3, pp. 197–200, 2005.
- Z. Y. Xie, D. F. Zhong, B. H. Yang, and X. Jin, Yaowu Fenxi Zazhi, vol. 24, pp. 1–4, 2004.
- Z. Xie, X. Chen, F. Jin, and D. Zhong, “Simultaneous determination of pantoprazole and Its two metabolites in dog plasma by HPLC,” Journal of Chromatographic Science, vol. 43, no. 5, pp. 271–275, 2005.
- C. V. Garcia, C. S. Paim, and M. Steppe, “New liquid chromatographic method for determination of rabeprazole sodium in coated tablets,” Journal of Association of Official Analytical Chemists International, vol. 87, no. 4, pp. 842–846, 2004.
- Y. Yokoyama, N. Kishi, H. Ohe, M. Tanaka, and N. Asakawa, “Fundamental processes for LC- NMR and its applications,” Analytical Sciences, vol. 19, no. 4, pp. 262–263, 1998.
- D. V. Bharathi, K. K. Hotha, B. Jagadeesh et al., “Simultaneous estimation of four proton pump inhibitors - Lansoprazole, omeprazole, pantoprazole and rabeprazole: development of a novel generic HPLC-UV method and its application to clinical pharmacokinetic study,” Biomedical Chromatography, vol. 23, no. 7, pp. 732–739, 2009.
- M. Noubarani, “Improved HPLC method for determination of four PPis, omeprazole, pantoprazole, lansoprazole and rabeprazole in human plasma,” Journal of Pharmacy and Pharmaceutical Sciences, vol. 13, no. 1, pp. 1–10, 2010.
- “Validationof analytical procedures: text and methodology,” http://www.ich.org/cache/compo/363-272-1.html#Q2A.