Translate this page into:
Copper(II)–neocuproine reagent for spectrophotometric determination of captopril in pure form and pharmaceutical formulations
*Corresponding author aymanchimca@yahoo.com (Ayman A. Gouda)
-
Received: ,
Accepted: ,
This article was originally published by Elsevier and was migrated to Scientific Scholar after the change of Publisher.
Available online 14 April 2010
Abstract
A simple, rapid, sensitive and accurate spectrophotometric method for the determination of captopril in pure form and pharmaceutical formulations is developed. The procedure is based on the reaction of copper(II) with captopril in the presence of neocuproine (NC) (2,9-dimethyl-1,10-phenanthroline) reagent in acetate buffer at pH 5.0. Copper(II) is reduced easily by captopril to Cu(I)–neocuproine complex, which shows an absorption maximum at 448 nm. Beer’s law was obeyed in the concentration range 0.3–3.0 μg mL−1 with a minimum detection limit (LOD) of 0.039 μg mL−1 and a quantification limit (LOQ) of 0.129 μg mL−1. For more accurate results, Ringbom optimum concentration ranges was 0.5–2.7 μg mL−1. The apparent molar absorbtivity and Sandell sensitivity were calculated. The validity of the proposed method was tested by analyzing the pure and pharmaceutical formulations and compared well with those obtained by the official method and demonstrated good accuracy and precision.
Keywords
Captopril
Neocuproine
Spectrophotometry
Pharmaceutical formulations
1 Introduction
Captopril, (Fig. 1), 1-(3-mercapto-2-d-methyl-1-oxoproppyl)-l-proline (S,S), is used therapeutically as an antihypertensive agent. It acts as a potent and specific inhibitor of angiotensin-converting enzyme. In addition, it is used in the management of heart failure, following myocardial infraction and in diabetic nephropathy. About 60–75% of a dose of CPL is absorbed from the gastro-intestinal tract and peak plasma concentration is achieved in about an hour. About 30% of the drug is bound to plasma protein (Parfitt et al., 1999). The drug is listed in United States Pharmacopoeia (United States Pharmacopoeia et al., 2004), which recommends an HPLC method for its assay in bulk and tablet formulations.
Several methods have been reported for the quantitative determination of CPL in dosage forms and biological fluids, including: GC–MS (Liu et al., 1995, 1998; Rose, 1998), HPLC (Huang et al., 2006; Nishikawa et al., 2004; El-Gindy et al., 2004; Russell et al., 1997; Bahmaei et al., 1997; Bald and Sypniewski, 1997; Kok et al., 1997; Favaro and Fiorani, 1996; Salazar et al., 1999; Battermann et al., 1998; Khedr and El-Sherief, 1998), electrochemistry (Stefan et al., 2000a; Stefan et al., 2000b; Fraga et al., 1998; Riberio et al., 2003), chemiluminescence (Ouyang et al., 1999), capillary electrophoresis (Hillaert and Van-den-Bossche, 1999), flow injection chemiluminescence (Li et al., 2001), titrimetry (El-Brashy, 1995), atomic absorption spectrophotometry (El-Reis et al., 2000) and several spectrophotometric methods have been reported in the literature (Askal, 1991; Sastry et al., 1991a; Mahadik et al., 1991; Sastry et al., 1991b; Albero et al., 1993; Ibraham, 1994; Jovanovic et al., 1995; Sastry et al., 1996; Huan et al., 2005; Sachan et al., 1997; Sastry et al., 1998; Gumieniczek et al., 1998; Karli´cˇek and Solich, 1998; El Walily et al., 1999; Shingare and Kale, 2000; Basavaiah et al., 2003a, b, c; Tzanavaras et al., 2003; Srivastava et al., 2003; Basavaiah and Nagegowda, 2004a; Basavaiah and Nagegowda, 2004b; Hosseinimehr et al., 2004; El-Shabrawy et al., 2004; Rahman et al., 2005; Huan et al., 2005; Shama et al., 2006; Chandru and Sharada, 2007; Suarez et al., 2007; Belal et al., 2008; Haggag et al., 2008; El-Enany et al., 2008). Comparison between the previous spectrophotometric methods for the determination of captopril are shown in Table 1. These methods suffer from a variety of disadvantages, such as use of sophisticated and time consuming techniques, require expensive instruments, low sensitivity, heating, extraction, require nonaqueous media and have higher Beer’s law ranges.
| Method | λmax (nm) | Beer’s law (μg mL−1) | Detection limits (μg mL−1) | Molar absorpitivity (l mol−1 cm−1) | Reference |
|---|---|---|---|---|---|
| FeCl3 + bipyridyl Residual iodine Residual iodine–starch complex |
523 351 620 |
0.25–25 | – | – | 26 |
| Palladium(II) chloride | 380 | up to 5 × 10−4 M | 2.17 | 1.875 × 103 | 32 |
| Ecess sodium nitrite/0.25 M HCl/cresyl fast violet acetate | 555 | 0.1–0.5 | 33 | ||
| Excess KBrO3 + celestine blue | 540 | 0.4–4.0 | 36 | ||
| Carbon disulphide + divalent metals: cobalt(II) Pallidium(II) Nikel(II) |
390 450 364 |
16–48 40–120 30–80 |
0.878 3.479 1.838 |
3.00 × 103 1.85 × 103 1.30 × 103 |
39 |
| Sodium metavanadate in acetic acid medium + ferroin | 510 | 2.5–20 | 0.18 | 7.31 × 103 | 44 |
| Excess of iodate in sulphuric acid medium. | 460 | range 50–400 | – | 0.38 × 103 | 46 |
| Excess of chloramine-T + metol and sulphanilic acid | 520 | 0–30 | 0.95 | 5.23 × 103 | 47 |
| Excess bromate–bromide reagent + methyl orange | 510 | 0.25–2.0 | – | 7.08 × 104 | 48 |
| DTNB reagent | 412 | 1–10 × 10−5 M | 3.2 × 10−7 M | 13,553 | 49 |
| Potassium iodate in HCl medium + CCl4 | 510 | 120–520 | – | – | 51 |
| Potassium permanganate in acidic medium + methylene blue (MB) Acid blue 74 (AB) Acid red 73 (AR) Amaranth dye (AM) Acid orange 7 (AO) |
660 610 510 520 485 |
0.4–12.5 0.3–10 0.5–11 0.4–8.3 0.5–9.3 |
0.106 0.063 0.145 0.093 0.134 |
1.74 × 104 2.98 × 104 1.87 × 104 2.63 × 104 2.35 × 104 |
53 |
| Hexacyanoferrate(III) | 510 | 0.25–12.00 | 0.08 | 9.14 × 103 | 55 |
| 2,4-Dinitrofluorobenzene (DNFB) | 2.4–16.8 | – | – | 56 | |
| 4-chloro-7-nitro-2,1,3-benzoxadiazole (NBD-Cl) | 420 | – | – | – | 57 |
| 2,6-dichloroquinone-4-chlorimide (DCQ) in dimethylsulphoxide. | 443 | 10–50 | 0.66 | – | 58 |
| Cu(II) + neocopoin | 448 | 0.3–3.0 | 0.056 | 4.223 × 104 | Present work |
The formation of the charge transfer complex between Cu(I) and neocuproine (NC) (2,9-dimethyl-1,10-phenanthroline) is the basis of the existing spectrophotometric method for the determination of trace amounts of reducing agents (Greenwood and Earnshaw, 1997). This was previously used to determine the biochemically important reductants such as cysteine (T¨utem and Apak, 1991), Vitamin E (T¨utem et al., 1997), ascorbic acid (Guclu¨ et al., 2005), isoniazide (Safavi et al., 2004), certain proton pump inhibitors (Syed and Syeda, 2007) and ceftazidime (Moreno and Salgado, 2008) can be determined by reduction of Cu(II), followed by treating the Cu(I) with chromogenic reagent neocuproine.
The aim of the present study is to apply simple, accurate, selective, reproducible, and high sensitivity spectrophotometric method of the determination of captopril in pure form and pharmaceutical formulations based on its reducing ability.
2 Experimental
2.1 Apparatus
All absorption spectra were made using Kontron 930 (UV–Visible) spectrophotometer (German) with a scanning speed of 200 nm/min and a band width of 2.0 nm, equipped with 10 mm matched quartz cells. Hanna pH-meter instrument (Portogal) (HI: 9321) was used for checking the pH measurements. All experiments were performed at 25 °C.
2.2 Materials
An authentic sample of captopril was kindly supplied by Bristol Myers Squibb Egypt Co., Giza, Egypt. The commercial preparations were bought from the local market.
2.3 Standard solutions
A stock solution 1000 μg mL−1 of captopril was prepared by dissolving 0.1 g of captopril in 100 mL of bidistilled water. The standard solution was stable for one week when kept in the refrigerator. Working standards were prepared by appropriately diluting the above solution with the same solvent.
2.4 Reagents
All reagents were of analytical reagent grade. Double distilled water was used throughout the study.
A stock solution 1.0 × 10−2 M of Cu(II) was prepared by dissolving 0.241 g of Cu(NO3)2·3H2O (Merck) in water and diluting to the mark in a 100 ml standard flask.
A 5.0 × 10−3 M stock solution of neocuproine hemihydrate (Merck) was prepared by dissolving 0.054 g of reagent in ethanol in a 50 mL standard flask and diluting to the mark with the same solvent.
Acetate buffer solutions of acetic acid–sodium acetate (pH 3.0–7.0) were prepared by following the standard methods. The pH of stock solution was adjusted to an appropriate value by addition of 0.2 M hydrochloric acid or sodium hydroxide with the help of pH meter (Perrin and Dempsey, 1974).
2.5 Recommended analytical procedure
Two mL of 5.0 × 10−3 M neocuproin solution, 1.0 mL of 1.0 × 10−2 M Cu(II) solution, 3.0 mL acetate buffer solution (pH 5.0) and a suitable volume (0.06–0.6 mL) of captopril standard solution 50 μg mL−1 were placed in a 10 mL volumetric flask and mixed. After 150 s, the absorption was measured at 448 nm against a neocuproin–copper(II) solution reagent blank.
2.5.1 Analysis of pharmaceutical formulations
Twenty tablets of the drug were weighed, grounded to a fine powder and mixed. A sample equivalent to approximately 10 mg of captopril was weighed accurately, transferred into a 100 mL calibrated flask and diluted to volume with water. Then, mixed well for 10 min using a magnetic stirrer to aid dissolution and filtered through a sintered glass crucible G4. An appropriate volume of the filtrate was diluted further with water so that the concentration of captopril in the final solution was within the working range. The recommended procedures under calibration curve were then performed.
3 Results and discussion
Captopril as all thiols was expected to undergo to some extent oxidative degradation such as the formation of disulphide and this suggests the investigation of an analytical procedure based on the specific reactivity of the thiol group.
The development of direct spectrophotometric methods for thiols is still a difficult task. The problem is to find a reaction that gives a minimum of side-products and interferences and a simple procedure.
Although reaction with Cu(II) ions is among the most commonly used procedures for determination of thiols, the only spectrophotometric method (Gawargious et al., 1976) utilizing this reaction is indirect and based on addition of excess Cu(II), collection of the Cu(I) mercaptide formed and spectophotometric measurement of the unreacted Cu(II) ions left in the solution:
The present work offers a quite different approach. When the copper(II)–neocuproine complex is used as the reagent, precipitation of Cu(I) mercaptide does not take place. Instead, the orange-yellow Cu(I)–neocupoine chelate is formed once, according to the equation:
The reduction of Cu(II) to Cu(I) in the presence of neocuproine and subsequent complex formation between Cu(I) and neocuproine takes few minutes to complete. Fig. 2 shows the changes of the absorbance at 448 nm with time during the first few minutes from initiation of the reaction. As it is obvious, the absorbance reaches a maximum after about 2 min and remains constant afterwards. Therefore, all the absorbance measurements were performed after 150 s from initiation of the reaction.
3.1 Absorption spectrum
The reagent blank does not absorb in the visible range of spectrum, but when captopril reacts with [Cu(NC)2]2+, an orange-yellow colored [Cu(NC)2]+, is formed which has an absorbance maximum at 448 nm and was stable for at least 2 h. The absorption spectra of the products and reagent blank are shown in Fig. 3.
3.2 Effect of experimental parameters
The effects of variables such as pH, concentration of neocuproine and Cu(II) were studied to establish the best reaction conditions for the maximum sensitivity.
3.2.1 Effect of pH
The effect of pH on the reduction of Cu(II) by captopril and formation of Cu(I)–neocuproine complex was studied over the pH range of (3.0–7.0) of acetate buffer solutions. Fig. 4 illustrates the effect of changing pH on the absorbance of the solution mixture. The absorbance increased with increasing pH up to 4.0 and remains constant to pH 6.0. Therefore, pH 5.0 was selected for further studies. The influence of pH on Cu(II) reduction by captopril is expected since captopril has a thiol group and H+ is involved in the oxidation–reduction process of this thiol group.
3.2.2 Effect of neocuproine concentration
The effect of neocuproine concentration was examined over the range 5 × 10−4 to 2.5 × 10−3 M. The results are shown in Fig. 5. As it can be seen, at high concentrations of neocuproine, the absorbance due to Cu(I)–neocuproine complex decreases. This might be due to the fact that high concentrations of neocuproine would result in a positive interference from Cu(II) which could have arisen from incomplete conversion of Cu(I) into the Cu(I)–neocuproine complex via mixed ligand complex formation, as suggested by T¨utem and Apak (1991). A 5.0 × 10−3 M neocuproine concentration was thus chosen as the optimum conditions.
3.2.3 Effect of Cu(II) concentration
The influence of Cu(II) concentration on the absorbance in the concentration range of 1.0 × 10−1 to 1.0 × 10−4 M of Cu(II) was shown in Fig. 6. The oxidising power of Cu(II) in a solution containing neocuproine is dependent on the ease of formation of [Cu(NC)2]+. An excess of Cu(II) can exhibit an affinity for neocuproine, thereby preventing the preferential quantitative formation of [Cu(NC)2]+. Thus, large excess of Cu(II) competes with Cu(I) for complex formation with neocuproine. A 1.0 × 10−2 M was selected as the optimum Cu(II) concentration.
3.3 Analytical performance
3.3.1 Method validation
The validity of the method was tested regarding linearity, specificity, accuracy, repeatability and precision according to ICH Q2B recommendations (Guidance for Industry Bioanalytical method Validation et al., 2001).
3.3.1.1 Linearity
The absorbance–concentration plot was rectilinear over the range of 0.3–3.0 μg mL−1 with a minimum detection limit of 0.039 μg mL−1. Linear regression analysis of the data gave the following equation:
Where, A is the absorbance in 1 cm cell and C is the concentration of the drug in μg mL−1 and r is the correlation coefficient.
The limit of quantification (LOQ) was determined by establishing the lowest concentration that can be measured according to ICH Q2B (Guidance for Industry Bioanalytical method Validation et al., 2001). The results are shown in Table 2. The limits of detection (LOD) were determined by establishing the minimum level at which the analyte can be reliably detected, and the results are also abridged in Table 2. LOQ and LOD were calculated according to the following equation (Guidance for Industry Bioanalytical method Validation et al., 2001):
| Parameters | Proposed method | Official method (2) |
|---|---|---|
| Wavelengths, λmax (nm) | 448 | |
| Beer’s law limits (μg mL−1) | 0.3–3.0 | |
| Ringbom limits (μg mL−1) | 0.5–2.7 | |
| Molar absorptivity ɛ, (L/mol−1 m−1) | 4.223 × 104 | |
| Sandell’s sensitivity (ng cm−2) | 5.15 | |
| Regression equation (y)a | ||
| Intercept (a) | 0.004 | |
| Slope (b) | 0.1877 | |
| Correlation coefficient (r) | 0.9998 | |
| LOD (μg mL−1) | 0.039 | |
| LOQ (μg mL−1) | 0.129 | |
| No. of experiments | 6 | 3 |
| Mean found (% ± SD) | 100.04 ± 0.75 | 99.89 ± 0.78 |
| RSD | 0.75 | 0.78 |
| RE | 0.307 | 0.45 |
| Variance | 0.56 | 0.61 |
| Calculated t-value (2.36)b | 0.23 | |
| Calculated F-value (5.79)b | 1.08 | |
RE, relative error; RSD, relative standard deviation; LOD, limit of detection; LOQ, limit of quantification; ɛ, molar absorptivity coefficient.
Where, σ: the standard deviation of the intercept of regression line. S: Slope of the calibration curve.
The proposed methods were evaluated for the accuracy as percent relative error (% RE) and the precision as percent relative standard deviation (% RSD) (Table 2). Statistical analysis (Miller and Miller, 2005) of the results, obtained by the official (United States Pharmacopoeia et al., 2004) and the proposed methods using student’s t-test and variance ratio F-test, show no significant difference between the performance of the two methods regarding the accuracy and precision, respectively (Table 2).
3.3.1.2 Precision, accuracy and specificity
In order to determine the accuracy and precision of the proposed methods, solutions containing four different concentrations of captopril were prepared and analyzed in six replicates. The relative standard deviation as precision and percentage relative error (Er%) as accuracy of the suggested method were calculated at 95% confidence level can be considered satisfactory. Precision was carried out by six determinations at four different concentrations. The percentage relative error calculated using the following equation:
The inter-day and intra-day precision and accuracy results are shown in (Table 3). The analytical results of accuracy and precision show that the proposed method has good repeatability and reproducibility.
| Taken (μg mL−1) | Inter-day | Intraday | ||||
|---|---|---|---|---|---|---|
| Recoverya (%) | Precision (RSD%)a | Accuracy (Er%) | Recoverya (%) | Precisiona (RSD%) | Accuracy (Er%) | |
| 0.5 | 98.94 | 1.12 | −1.06 | 99.90 | 0.66 | −0.10 |
| 1.0 | 99.57 | 0.92 | −0.43 | 99.92 | 0.90 | −0.08 |
| 2.0 | 99.92 | 0.81 | −0.08 | 99.30 | 0.45 | −0.70 |
| 3.0 | 100.20 | 0.108 | 0.20 | 100.15 | 1.17 | 0.15 |
| 0.5 | 98.94 | 1.12 | −1.06 | 99.90 | 0.66 | −0.10 |
RSD%, percentage relative standard deviation.
Er%, percentage relative error.
3.3.1.3 Robustness of the method
The robustness of the method adopted is demonstrated by the constancy of the absorbance with the deliberated minor changes in the experimental parameters such as pH, volume of NC, 2.0 ± 0.2 mL, and change in the volume of Cu(II) (1.0 × 10−2 M), ±0.1 mL. These minor changes that may take place during the experimental operation did not affect the absorbance of the reaction product.
3.4 Effects of interference
The criterion of interference was an error of not more than ±3.0% in the absorbance. To test the efficiency and selectivity of the proposed method to pharmaceutical formulations. A systematic quantitative study was undertaken by measuring the absorbance of solutions containing 3.0 μg mL−1 of captopril by varying the additives and excipient such as glucose, lactose, fructose, calcium, hydrogen phosphate, magnesium stearate and starch. The excipients present in all tablets are not interfering for drug. Hydrochlorothiazide which is frequently co formulated with captopril in capozide and farcopril plus tablets did not interfere with the proposed method.
3.5 Analytical applications
The proposed method was applied to the determination of captopril in commercial tablets. Common tablet excipients did not interfere with the assay. Moreover, to check the validity of the proposed method, dosage forms were tested for possible interference with standard addition method. The performance of the proposed methods was assessed by calculation of the t-test (for accuracy) and a variance ratio F-value (for precision) compared with the official method (United States Pharmacopoeia et al., 2004). (for 95% confidence level with five degrees of freedom (Miller and Miller, 2005)).
The results showed that the t- and F-values were less than the critical value, indicating that there was no significant difference between the proposed and reference method (Sastry et al., 1996) for captopril as shown in Table 4. Because the proposed method was more reproducible with high recoveries than the reference method, they can be recommended for the routine analysis in the majority of drug quality control laboratories.
| Preparations | Taken (μg mL−1) | Added (μg mL−1) | Recoverya (%) | |
|---|---|---|---|---|
| Proposed method | Reference method Sastry et al. (1996) | |||
| Capoten tabletsb (25 mg captopril/tablet) | 0.5 | – | 100.90 | |
| 0.5 | 101.20 | |||
| 1.0 | 101.05 | |||
| 1.5 | 101.30 | |||
| 2.0 | 99.80 | |||
| 2.5 | 100.50 | |||
| Mean ± SD | 101.09 ± 0.37 | 101.99 ± 0.54 | ||
| te | 3.07 | |||
| Fe | 2.13 | |||
| Farcopril plus tabletsc (50 mg captopril and 25 mg of hydrochlorothiazide/tablet) | 0.5 | – | 99.55 | |
| 0.5 | 99.95 | |||
| 1.0 | 100.05 | |||
| 1.5 | 99.25 | |||
| 2.0 | 98.85 | |||
| 2.5 | 100.20 | |||
| Mean ± SD | 99.64 ± 0.52 | 100.48 ± 0.85 | ||
| te | 1.62 | |||
| Fe | 2.67 | |||
| Capozide tabletsd (25 mg captopril and 12.5 mg of hydrochlorothiazide/tablet) | 0.5 | – | 99.60 | |
| 0.5 | 100.45 | |||
| 1.0 | 100.15 | |||
| 1.5 | 100.30 | |||
| 2.0 | 99.85 | |||
| 2.5 | 98.70 | |||
| Mean ± SD | 101.01 ± 0.65 | 101.99 ± 0.54 | ||
| te | 2.59 | |||
| Fe | 1.45 | |||
4 Conclusions
A Cu(II)–neocuproine proved to be a suitable reagent for the determination of captopril in pure form and its pharmaceutical preparations. The high molar absorpitivity (ɛ) of the proposed method is a decisive advantage since the interference from associated excipients was not observed. The proposed method is simple, time saving and reproducible. Thus, the proposed method can be used as an alternative for rapid and routine determination of captopril in bulk samples and various pharmaceutical formulations in quality control and industry.
References
- J. Pharm. Biomed. Anal.. 1993;11:887.
- Talanta. 1991;38:1155.
- J. Pharm. Biomed. Anal.. 1997;15:1181.
- J. Anal. Chem.. 1997;358:554.
- Oxid. Commun.. 2004;27:203.
- Oxid. Commun.. 2004;27:186.
- Indian Pharm.. 2003;2:61.
- Oxid. Commun.. 2003;26:307.
- Bulg. Chem. Commun.. 2003;35:54.
- Oxid. Commun.. 2003;26:432.
- Laborpraxis. 1998;22:32.
- J. Food Drug Anal.. 2008;16:26.
- E-J. Chem.. 2007;4:216.
- J. Pharm. Biomed. Anal.. 1999;21:439.
- Acta Pharm. Hung.. 1995;65:91.
- Int. J. Biomed. Sci.. 2008;4:147.
- Farmaco. 2004;59:703.
- J. Pharm. Biomed. Anal.. 2000;23:249.
- Farmaco. 2004;59:803.
- Anal. Chim. Acta. 1996;332:249.
- Talanta. 1998;46:75.
- Gawargious, Y.A., Boulos, L.S., Faltaoos, B.N., 1976. Mikrochim. Acta (Wien) 11, 327.
- Greenwood, N.N., Earnshaw, A., 1997. Chemistry of the Elements, second ed. Butter-worth, Heinemann, p. 427.
- Guclu¨, K., Sozgen, K., Tutem, E., Ozyurek, M., Apak, R., 2005. Talanta 65, 1226.
- Guidance for Industry Bioanalytical method Validation, 2001. US Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research, Rockville, MD. <http://www.fda.gov/eder/guidance/4252fnl.pdf> (accessed 09.01.04).
- Acta Pol. Pharm.. 1998;55:21.
- Scientia Pharmaceutica. 2008;76:33.
- J. Pharm. Biomed. Anal.. 1999;21:65.
- Bollettino Chimico Farmaceutico. 2004;143:249.
- Pharm. Biomed. Anal.. 2005;37:219.
- J. Pharm. Biomed. Anal.. 2005;37:219.
- J. Pharm. Biomed. Anal.. 2006;41:644.
- Alex. J. Pharm. Sci.. 1994;8:229.
- J. Pharm. Biomed. Anal.. 1995;13:213.
- Karli´cˇek, R., Solich, P., 1998. Pharmazie 53, 549.
- Biomed. Chromatogr.. 1998;12:57.
- J. Chromatogr. Biomed. Appl.. 1997;693:181.
- Li, B., Zhang, Z., Wu, M., 2001. Microchem. J. 70, 85.
- Anal. Lett.. 1995;28:1465.
- Sepu. 1998;16:82.
- Indian Drugs. 1991;28:530.
- Miller, J.N., Miller, J.C., 2005. Statistics and Chemometrics for Analytical Chemistry, fifth ed. Prentice Hall, England, p. 256.
- Anal. Lett.. 2008;41:2143.
- Anal. Sci.. 2004;20:1395.
- Anal. Chim. Acta. 1999;386:257.
- Parfitt, K., 1999. Martindale, The Complete Drug Reference, 32nd ed., vol. 720. The Pharmaceutical Press, Massachusetts, p. 836.
- Perrin, D.D., Dempsey, B., 1974. Buffers for pH and Metal Ion Control. Wiley, New York, p. 134, 147, 149 (Chapter 10).
- Farmaco. 2005;60:569.
- Eclet. Quim.. 2003;28:39.
- J. Pharm. Biomed. Anal.. 1998;18:1.
- J. Pharm. Biomed. Anal.. 1997;15:1757.
- Indian Drugs. 1997;34:168.
- Spectrochim. Acta Part A. 2004;60:765.
- J. Chromatogr. Sci.. 1999;37:469.
- Pharmazie. 1991;46:465.
- Indian Drugs. 1991;28:523.
- Anal. Lett.. 1996;29:1329.
- Anal. Lett.. 1998;31:263.
- J. Quant. Spectro. Rad. Trans.. 2006;102:261.
- Indian Drugs. 2000;37:204.
- Indian J. Chem. – Section A Inorg., Phys., Theor. Anal. Chem.. 2003;42:3036.
- Anal. Chim. Acta. 2000;411:51.
- Talanta. 2000;51:969.
- J. Braz. Chem. Soc.. 2007;18:1215.
- Bull. Chem. Soc. Ethiop.. 2007;21:315.
- T¨utem, E., Apak, R., 1991. Anal. Chim. Acta 255, 121.
- T¨utem, E., Apak, R., G¨unaydı, E., S¨ozgen, K., 1997. Talanta 44, 249.
- Mikrochim. Acta. 2003;142:55.
- The United States Pharmacopoeia, 2004. USP 27 NF 22 Washington, 1, Convention, National Formulary, Asian Edition. Rockville, MD, p. 1068.
