Cefadroxil is an antibiotic [1] consumed and used to treat mild to moderate infections caused by susceptible microorganisms [2]. It is used to treat bacterial infection of the skin and strep throat for the urinary tract [3,4]. Figure 1 shows the structure of the drug.

Figure 1. Structure of Cefadroxil [5]

Several scientific methods of analysis were available in the literature for the determination of cefadroxil in their pharmaceutical preparations, including fluorimetry [6] and polarography [7,8]. Thin layer chro- matography [9], HPLC [10,11], sequential injection analysis [12], chemiluminescence [13,14], capillary electrophoresis [15], and spectrophotometric methods have been described to determine cefadroxil using various reagents based on the formation of complexes with copper (II) [16] Flow injection analysis (FIA) [17]. Additionally, another method is based on the liberation of hydrogen sulfide and followed by the reaction with N,N-diethyl-p-phenylenediamine [18].

Other spectrophotometric methods are reported for the determination of cefadroxil based on its reactivity with iodine [19]. Nitrosation and subsequent metal chelation reaction with 2,6-dichloro-quinone-4-amino-antipyrene in the presence of potassium hexacyanoferrate [20] or by oxidation in an acid medium [21].

These methods are time-consuming and required extraction steps or required indirect procedures. This work describes a simple and sensitive spectrophotometric method for the determination of cefadroxil. This method is based on the reaction of the drug with NQS and the formation of Schiff's base.

Experimental Apparatus

• Spectrophotometer using Ajena model 1100 (Germany) with a quartz cell with 1 cm path length, PW “9421” pH meter for a common glass electrode.

A meter electrical balance was used to weigh the sample. The reagent was supplied by BOH and Fluka. The standard solution of 100 ppm cefadroxil was prepared by dissolving 0.01 g in 2 ml of de-ionized water and then diluted to 100 ml. Also, 5 × 10-3 M of 1,2-naphthoquinone reagent was made by dissolving 0.06 g in 50 ml de-ionized water.

Results and Discussion

Study of Optimal Reaction Conditions

Impact of NQS Reagent

The impact of changing the reagent 1,2-naphthoquinone solution concentration onthe absorbance of cefadroxil was performed. It was noticed that the absorbance increasedand reached a maximum when 1 ml of 5 ×10 ^-3 M 1,2 - naphthoquinone solution wasused (Figure 2).

Figure 2. Impact of NQS Reagent Conc.

Impact of Base

The impact of bases (sodium hydroxideNaOH, potassium hydroxide KOH,ammonium hydroxide NH ₄ OH, and sodiumcarbonate Na ₂ CO ₃ ) was investigated. It wasfound that potassium hydroxide gave maximum absorption at 460 nm (Figure 3).

Figure 3. Bases (1 ml of 0.1M)

Furthermore, the impact of the potassium hydroxide volume and pH were studied. Maximum absorbance was observed when 1.5 ml of 0.1M KOH at pH 11.31 was used.

Table 1. The Impact of Increasing pH and the Volume of KOH 0.1 M on the Absorption of the Mixture (8 ppm Cefadroxil, NQS, KOH)

Impact of Surfactants

The impact of Tween 80 (TW-80), Triton X- 100 (TX-100), and cetyltrimethyl ammonium bromide (CTAB) of 0.1% concentration was studied. However, the absorbance was decreased when CTAB was used (Figure 4). Therefore, it was excluded from the experiment.

Figure 4. Impact of Surfactant on the Absorption of the Product

Impact of Temperature Versus Time on the Absorbance of the Complex

The effect of reaction time was performed at different temperatures. Figure 5 shows a decrease in the absorbance when time increased, attributed to the dissociation of the complex. It was found that the optimum time and temperature for the complex was 15 min at 40°C, respectively.

Figure 5. The Impact of Temperature Development and Time on the Stability of the Complex

Figure 6. Impact of the Order of Addition on the Absorption

Impact of the Order of Addition

Under the optimum conditions, the order of addition was investigated. Figure 6 shows that in the order of addition, no. II was the best.

Absorption Spectra

Figure 7 shows the absorption spectra for the best condition that has been confirmed above.

The Details of the Statistical Data and Optical Characteristics of the Suggested Method

The absorbance of the complex was measured at 460 nm. Beer's law limits and molar absorptivity values are shown in Table 2. In addition, the relative standard deviation (RSD) and the accuracy of analysis on six replicates for three different concentrations of cefadroxil indicate that the method is valid. Also, the limit of detection (LOD) is accepted as well.

Table 2. The Summary of Optical Characteristics

Analytical Implementation

The results showed that the experimental F-Test and T-Test were less than the theoretical value (t = 2.50, f = 6.41). However, it was observed that there was no significant variation between the suggested method and the formal method [22].

Quantities and Stability Constant

Quantities of a reaction of cefadroxil for NQS were studied through the molar ratio as well as job method [23,24].

Figure 8 (a) and (b) showed that the results were 1:1 and the average conditional stability constant for the resulting complex was calculated using the equation (1) below:

where K _st : the stability constant (L/mol), (∝): the dissociation degree, and (C): the concentration of the resulting complex. The average K _st is 2.7 × 10 ⁶ which illustrates that the resulting product is stable.

Mechanism of the Reaction

Under the experimental conditions, the mechanism of the reaction is shown in Scheme 1.

The mechanism suggests that the NQS was converted into a quinoidal which reacts with phenol amine via the replacement of the hydrogen atom of the primary aromatic amine group to produce paraquinoidimide- condensation (Schiff's base) NaHSO ₃ .

Conclusion

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