Hanan A. Merey

Spectrophotometric methods for simultaneous determination of ternary mixture of amlodipine besylate, olmesartan medoxomil and hydrochlorothiazide.

Four, accurate, precise, and sensitive spectrophotometric methods are developed for the simultaneous determination of a ternary mixture containing amlodipine besylate (AM), olmesartan medoxomil (OL) and hydrochlorothiazide (HZ), where AM is determined at its λ(max) 364.6 nm ((0)D), while (OL) and (HZ) are determined by different methods. Method (A) depends on determining OL and HZ by measuring the second derivative of the ratio spectra ((2)DD) at 254.4 and 338.6 nm, respectively. Method (B) is first derivative of the double divisor ratio spectra (D-(1)DD) at 260.4 and 273.0 nm for OL and HZ, respectively. Method (C) based on successive spectrophotometric resolution technique (SSRT). The technique starts with the ratio subtraction method then measuring OL and HZ at their isoabsorptive point at 260.0 nm, while HZ is measured using the amplitude of first derivative at 335.2 nm. Method (D) is mean centering of the ratio spectra (MCR) at 252.0 nm and 220.0 nm for OL and HZ, respectively. The specificity of the developed methods is investigated by analyzing laboratory prepared mixtures containing different ratios of the three drugs and their combined dosage form. The obtained results are statistically compared with those obtained by the official or reported methods, showing no significant difference with respect to accuracy and precision at p=0.05.

Development and Validation of a Stability-Indicating Micellar Liquid Chromatographic Method for the Determination of Timolol Maleate in the Presence of Its Degradation Products

A stability-indicating micellar liquid chromatographic (MLC) method was developed and validated for the quantitative determination of timolol maleate (TM) in the presence of its degradation products resulting from accelerated degradation in a run time not more than 8 min. TM was subjected to stress conditions of hydrolysis (including alkaline, acidic and thermal hydrolysis) and oxidation. An isocratic, rapid and mobile phase saving the micellar LC method was developed with a BioBasic phenyl column (150 × 1.0 mm, 5 µm particle size) and a micellar mobile phase composed of 0.1 M sodium dodecyl sulfate, 10% of 1-propanol and 0.1% of triethylamine in 0.035 M ortho-phosphoric acid. The flow rate of the mobile phase was 0.1 mL/min. UV detection was adjusted at 298 nm and performed at room temperature. The method has been validated according to the International Conference on Harmonisation guidelines. The method is successfully applied for the determination of TM in bulk powder and pharmaceutical dosage form.

Simultaneous determination of Fluticasone propionate and Azelastine hydrochloride in the presence of pharmaceutical dosage form additives.

Fluticasone propionate (FLU) and Azelastine hydrochloride (AZE) are co-formulated with phenylethyl alcohol (PEA) and Benzalkonium chloride (BENZ) (as preservatives) in pharmaceutical dosage form for treatment of seasonal allergies. Different spectrophotometric methods were used for the simultaneous determination of cited drugs in the dosage form. Direct spectrophotometric method was used for determining of AZE, while Derivative of double divisor of ratio spectra (DD-RS), Ratio subtraction coupled with ratio difference method (RS-RD) and Mean centering of the ratio spectra (MCR) are used for the determination of FLU. The linearity of the proposed methods was investigated in the range of 5.00-40.00 and 5.00-80.00μg/mL for FLU and AZE, respectively. The specificity of the developed methods was investigated by analyzing laboratory prepared mixtures containing different ratios of cited drugs in addition to PEA and their pharmaceutical dosage form. The validity of the proposed methods was assessed using the standard addition technique. The obtained results were statistically compared with those obtained by official or the reported method for FLU or AZE, respectively showing no significant difference with respect to accuracy and precision at p=0.05.

Simultaneous Determination of Timolol maleate and Brimonidine tartarate in their Pharmaceutical Dosage Form

Abstract Three new simple and selective assays were developed for the analysis of binary mixture containing timolol maleate (TM) and brimonidine tartarate (BT) in the presence of benzalkonium chloride (BZ) as a preservative in eye drops. The first derivative ultraviolet spectrophotometry was used with zero-crossing measurements at 313 nm for TM and 386 nm for BT, respectively. The second method depends on the first derivative of the ratio spectra with zero-crossing measurements at 313 nm and 391 nm for TM and BT, respectively using 0.25 µg/mL BZ as a divisor. The assays were linear over the concentration ranges 5–85 µg/ mL and 2–35 µg/mL for TM and BT, respectively. The third method was based on isocratic and mobile phase saving micellar liquid chromatographic method with a Biobasic phenyl column (150 x 1.0 mm, 5 µm particle size) and micellar mobile phase composed of 0.1M SDS, 10 % of 1-propanol and 0.1 % of TEA in 0.035M ortho phosphoric acid. UV detection was adjusted at 298 nm and 250 nm for TM and BT, respectively performed at room temperature. The linearity range for TM and BT was 2–100 µg/mL and 1–50 µg/mL, respectively. The proposed methods showed high percentage recovery, good accuracy and precision.

Validated simultaneous determination of antipyrine and benzocaine HCl in the presence of benzocaine HCl degradation product

Two validated, sensitive and highly selective stability-indicating methods were adopted for the simultaneous quantitative determination of antipyrine (ANT) and benzocaine HCl (BEN) in the presence of the degradation product of benzocaine HCl [p-aminobenzoic acid (PABA)]. The first method was high performance liquid chromatography, where a mixture of antipyrine (ANT), benzocaine HCl (BEN) and degradation product of benzocaine HCl (PABA) is separated on a C8 ZORBAX analytical column (5 μm, 4.6 × 150 mm I.D.) using acetonitrile–phosphate buffer of pH 5.5 (25 : 75, v/v) as the mobile phase. The drugs were detected at 270 nm over a concentration range of 10–100 μg mL−1 and 5–100 μg mL−1, with mean percentage recoveries of 100.22% (S.D. 1.375) and 99.77% (S.D. 1.089) for antipyrine and benzocaine HCl, respectively. The second method was thin layer chromatography combined with the densitometric determination of the separated bands at 275 nm. Adequate separation was achieved using silica gel 60 TLC F254 plates and toluene–acetone–methanol–ammonia (8 : 3 : 3 : 0.1 by volume) as the mobile phase. The proposed methods were applied for the analysis of antipyrine and benzocaine HCl in their pharmaceutical formulation, and the results were statistically compared with the reported methods.

SIMULTANEOUS DETERMINATION OF PRAMOCAINE HCL AND HYDROCORTISONE ACETATE IN PHARMACEUTICAL DOSAGE FORM

Two sensitive and selective methods were developed and validated for simultaneous determination of pramocaine HCl and hydrocortisone acetate in pharmaceutical dosage form. The first method is a spectrodensitometric method where pramocaine HCl and hydrocortisone acetate were separated using toluene:methanol:chloroform: 10% NH3 [(5:3:6:0.1, by volume) as the developing system followed by densitometric measurement at 290 nm] and 250 nm for pramocaine HCl and Hydrocortisone acetate, respectively. The second method is a high performance liquid chromatographic method for separation and determination of both drugs using reversed phase C18 column and mobile phase consisting of distilled water:acetonitrile:triethylamine (530:470:0.1, by volume); pH was adjusted to 3 by o-phosphoric acid. The proposed methods were successfully applied for the analysis of pramocaine HCl and hydrocortisone acetate in laboratory prepared mixtures and in pharmaceutical dosage form and the results obtained were assessed by applying the standard addition technique. Statistical comparison between the results obtained by applying the proposed methods and official method for the cited drugs was done and no significant difference was found at p = 0.05.

Spectrophotometric Methods for Simultaneous Determination of Oxytetracycline HCl and Flunixin Meglumine in Their Veterinary Pharmaceutical Formulation

Four precise, accurate, selective, and sensitive UV-spectrophotometric methods were developed and validated for the simultaneous determination of a binary mixture of Oxytetracycline HCl (OXY) and Flunixin Meglumine (FLU). The first method, dual wavelength (DW), depends on measuring the difference in absorbance (ΔA 273.4–327 nm) for the determination of OXY where FLU is zero while FLU is determined at ΔA 251.7–275.7 nm. The second method, first-derivative spectrophotometric method (1D), depends on measuring the peak amplitude of the first derivative selectively at 377 and 266.7 nm for the determination of OXY and FLU, respectively. The third method, ratio difference method, depends on the difference in amplitudes of the ratio spectra at ΔP 286.5–324.8 nm and ΔP 249.6–286.3 nm for the determination of OXY and FLU, respectively. The fourth method, first derivative of ratio spectra method (1DD), depends on measuring the amplitude peak to peak of the first derivative of ratio spectra at 296.7 to 369 nm and 259.1 to 304.7 nm for the determination of OXY and FLU, respectively. Different factors affecting the applied spectrophotometric methods were studied. The proposed methods were validated according to ICH guidelines. Satisfactory results were obtained for determination of both drugs in laboratory prepared mixture and pharmaceutical dosage form. The developed methods are compared favourably with the official ones.

Spectrophotometric and Chemometric Study for the Simultaneous Determination of Mometasone Furoate and Miconazole Nitrate in the presence of Pharmaceutical Dosage Form Additive

Abstract Mometasone Furoate (MO) and Miconazole Nitrate (MI) are co-formulated with p-chloro-meta-cresol (CMC) which added in pharmaceutical dosage form as a preservative together for treatment of skin infections by candida or dermatophyte in which inflammatory and pruritic manifestation are prominent. Comparative study between different specrtophotometric methods were done for the simultaneous determination of cited drugs in the dosage form. Spectrophotometric methods were used including, derivative ratio spectra (DD), derivative of double divisor of ratio spectra (DD-RS) and Mean centering of the ratio spectra (MCR). While the chemometric methods were used including, partial least-squares (PLS) and principal component regression (PCR). The linearity of the proposed methods was investigated in the range of 3–33 and 60–840μg/mL for MO and MI, respectively. The specificity of the developed methods was investigated by analyzing laboratory prepared mixtures containing different ratios of cited drugs in addition to CMC and their pharmaceutical dosage form. The validity of the proposed methods was assessed using the standard addition technique. The obtained results were statistically compared with those obtained by the reported method, showing no significant difference with respect to accuracy and precision at p=0.05.