Comparative study of extension area based methods for spectrophotometric determination of desmopressin acetate in the presence of its acid-induced degradation products

Abstract

Desmopressin acetate (DPA) is a synthetic analogue of vasopressin used in the treatment of diabetes insipidus, bedwetting, hemophilia A, and elevated levels of urea in the blood. Sensitive and selective stability-indicating methods are needed to be developed and validated for its assay pure and pharmaceutical dosage forms in the presence of its degradation products as no method has been reported for its determination in the presence of its degradants. This work describes a comparative study of five simple stability-indicating spectrophotometric techniques for determination of DPA in presence of its acid-degradation products (acid-degradants) without prior separation. The proposed spectrophotometric techniques (First derivative, Derivative ratio, Ratio difference, Mean centering and Dual wavelength) were developed and validated according to ICH guidelines. Acid degradation was carried out with 0.1 N HCl; the acid-degradants were separated on TLC plates and the acidic degradation pathway was established by IR, H-NMR and MS techniques. The TLC method was based on the separation of DPA and its acid-induced degradation products on silica gel plates using methanol: water (80:20, v/v) as a developing system and UV detection at 254 nm. All assay suggested methods were successfully applied for quantitation of DPA in pure and tablet forms. They are specific, sensitive, precise and accurate. They showed good linearity in the concentration range of 1–14 µg/mL with good correlation coefficients, and limit of detection (LOD) of 0.304, 0.274, 0.167, 0.248 and 0.199 and limit of quantitation (LOQ) of 0.920, 0.829, 0.506, 0.751 and 0.604) for each method, respectively. These methods were successfully applied for the simultaneous determination of DPA in its pure and tablet dosage form in the presence of its acid-degradants. The results obtained were statistically comparable with those of reported HPLC assay method; no significant differences were observed with relevance to accuracy and precision. All the methods are sensitive, selective and can be used for the routine analysis of DPA in its pure and dosage forms.

Chromatographic reversed HPLC and TLC-densitometry methods for simultaneous determination of serdexmethylphenidate and dexmethylphenidate in presence of their degradation products—with computational assessment

“…After complete separation, each degradant was scratched and extracted twice with methanol and dried at 25–30 °C to obtain pure solid form. Isolated degradants were subsequently subjected to infrared/nuclear magnetic resonance/mass spectral analyses for identification [ 10 , 11 ].…”

“…Complete degradation was verified by TLC plate using methanol: chloroform (70:30 v/v) as a mobile phase. Each sample was then neutralized with 0.1N alkali or 0.1N acid, evaporated to dryness, and dissolved by 50 mL of methanol, transferred into 100 mL volumetric flask, and completed to the mark with methanol to obtain a stock concentration equivalent to 250 μg/ mL of each drug degradant [9][10][11].…”

Continuous wavelet transform for solving the problem of minor components in quantitation of pharmaceuticals: a case study on the mixture of ibuprofen and phenylephrine with its degradation products

“…Wahbi et al [ 12 ] applied Fourier functions for spectrophotometric quantitation of mixtures (discrete Fourier transform). Mean centering was also introduced as a processing technique for ratio spectra, and it was applied for the analysis of binary and ternary mixtures [ 13 – 15 ]. Finally, wavelet transform represents a powerful tool for signal processing that can be used for spectrophotometric analysis of mixtures [ 16 ].…”