Smart stability indicating spectrophotometric methods for determination of modafinil: the promising treatment for post-covid neurological syndrome

Abstract

Modafinil (MDF) is one of the neurostimulants with a potential effect in the COVID-19 ICU ventilated patients and post-COVID neurological syndrome treatment. Four rapid, simple and cost-effective stability indicating spectrophotometric methods were used for estimation of MDF in the presence of its acidic degradation product, namely; ratio difference (RD), first derivative of the ratio spectra (¹DD), mean centering (MCR) and ratio subtraction method (RS). These methods were validated according to ICH guidelines and all methods revealed a good linearity in concentration range of (5-30 µg/mL) in addition to a good accuracy and precision with mean percentage recovery of 99.97 ± 0.305 for (RD), 100.10 ± 0.560 for (¹DD), 100.02 ± 0.483 for (MCR) & 99.18 ± 1.145 for (RS) method. Specificity of the proposed methods was assessed and MDF was determined in the presence of up to 80% of its acidic degradation product for RD, ¹DD, MCR and RS methods. The proposed methods were successfully applied for the determination of MDF in bulk powder and its tablet dosage form with mean percentage recovery of 100.33 ± 0.915 for (RD), 100.62 ± 0.985 for (¹DD), 99.70 ± 0.379 for (MCR) and 100.21 ± 0.313 for (RS) method. The results obtained were statistically compared with those of official HPLC method and showed no significant difference with relevance accuracy and precision.

Keywords: Derivative ratio; Mean centering; Modafinil; Ratio difference; Ratio subtraction.

Fig. 1

Chemical structure of Modafinil

Fig. 2

Zero order absorption spectra of (10 µg/mL) modafinil (–) and (70 µg/mL) of its acidic degradation (-—-) in methanol

Fig. 3

Ratio spectra of modafinil 5-30 µg/mL(–) and 50 µg/mL of its acidic degradation product (-—-) using 70 µg/mL of degradation as a divisor in methanol

Fig. 4

First derivative of ratio spectra of 5-30 µg/mL modafinil (–) and 50 µg/mL of degradation product (—) using 70 µg/mL of degradation as a divisor at (241.8 nm) in methanol

Fig. 5

Mean centering of ratio spectra of MDF 5-30 µg/mL using the spectrum of 70 µg/mL of degradation as a divisor at 226 nm in methanol

Fig. 6

A Ratio spectra of laboratory prepared mixtures of modafinil and its degradation product using 70 µg/mL of its degradation product as a divisor. B The obtained ratio spectra after subtraction of the constant. C The obtained spectra of modafinil after multiplication by the divisor. D Second derivative of the obtained spectra of the laboratory prepared mixtures