Generic daclatasvir plus sofosbuvir, with or without ribavirin, in treatment of chronic hepatitis C: real-world results from 18 378 patients in Egypt.

BACKGROUND: Treatment of chronic hepatitis C using combination of sofosbuvir (SOF) and daclatasvir (DCV) was used in several clinical trials and multicentre studies, which were somewhat limited to genotypes 1-3. The national program in Egypt is using SOF-DCV combination for large scale treatment. AIM: To assess the efficacy and safety of combined SOF-DCV in treating patients with HCV-G4 in a real-world setting. METHODS: Data and outcome of chronic HCV patients who were treated for 12 weeks with generic medications: DCV 60 mg plus SOF 400 mg ± ribavirin (RBV) within the national hepatitis C treatment program in Egypt are presented. Treatment-naïve patients without cirrhosis were treated without RBV, and those who had cirrhosis or were treatment-experienced (interferon experienced or SOF experienced) received RBV. Efficacy and safety were assessed, and baseline factors associated with sustained virological response at post-treatment week 12 (SVR12) were explored. RESULTS: During the first 2 months of the programme, 18 378 patients with HCV-G4 started treatment with SOF-DCV with or without RBV. Overall, 95.1% achieved SVR12 (95.4% among patients treated without RBV and 94.7% for patients treated with RBV, P = .32). Treatment was prematurely discontinued in only 1.5% of patients. The most common events leading to discontinuation were patient withdrawal (n = 76) and pregnancy (n = 5). Five deaths occurred within this group. CONCLUSIONS: Real-world experience of generic SOF-DCV in patients with chronic HCV-G4 proved to be safe and associated with a high SVR12 rate, in patients with different stages of fibrosis.

First derivative spectrophotometric and high-performance liquid chromatographic determination of cinchocaine hydrochloride in presence of its acid degradation product.

Two methods are presented for the determination of cinchocaine HCl in presence of its acid-induced degradation product using first (1D) derivative spectrophotometry and high-performance liquid chromatography. Cinchocaine HCl was determined by measurement of its first derivative amplitude at the zero crossing point of 2-hydroxyquinoline-4-carboxylic acid diethylaminoethylamide as its acid degradation product (at 333.5 nm). The HPLC method depends upon using a mu Bondapak C18 column at ambient temperature with a mobile phase consisting of acetonitrile--0.01 M sodium acetate trihydrate (45:55, v/v) containing 0.06% (w/v) heptane sulphonic acid sodium salt and adjusted to apparent pH 4.5 with acetic acid at a flow rate 2 ml min-1. Quantitation was achieved with UV detection at 254 nm based on peak area. The HPLC method was applied for simultaneous determination of cinchocaine HCl, methylparaben and propylparaben. The two proposed methods were successfully applied to the determination of the cinchocaine HCl in laboratory-prepared mixtures in the presence of its acid degradation product and in cream. Moreover, the proposed methods were utilized to investigate the kinetics of the acid degradation process at different temperatures and the apparent pseudo first-order rate constant, half-life and activation energy calculated.

Spectrophotometric and high performance liquid chromatographic determination of cetirizine dihydrochloride in pharmaceutical tablets.

Derivative spectrophotometric, colorimetric and high performance liquid chromatographic methods, for the determination of the antihistaminic cetirizine dihydrochloride in tablet form were described. Spectrophotometrically, cetirizine was determined by the measurement of its first (1D) and second (2D) derivative amplitudes at 239 (peak) and 243-233 nm (peak-to-trough), respectively. The aqueous solutions obeyed Beer's law in the concentration ranges of 1.2-10.0 and 0.8-10.0 micrograms ml-1 for 1D and 2D measurements, respectively. The colorimetric procedure was based on measuring the absorbency of the coloured chromogen resulted from the reaction between cetirizine sodium salt in polar solvent (DMF) and chloranil at 556 nm. The relation with concentrations was linear over 120-250 micrograms ml-1. Optimization of the reaction conditions was studied. At the same time, investigation of the complex formed was made with respect to its composition and the associated constant. A simple liquid chromatographic assay has been developed for the determination of cetirizine dihydrochloride in the presence of one of its synthesis precursor (hydroxyzine hydrochloride). A Bondapak-C18 column was used with a mobile phase consisting of acetonitrile/0.01 M ammonium dihydrogen phosphate (32:68, v/v) containing 0.1% w/v tetrabutyl ammonium hydrogen sulphate adjusted to pH 3 with phosphoric acid at a flow rate of 2 ml min-1. With salicylic acid as internal standard, quantitation was achieved with UV detection at 230 nm based on the peak height ratios. Beer's law was obeyed in a concentration range of 3-35 micrograms ml-1 and the regression line equation was derived with a correlation coefficient of 0.9999. The validity of the methods was further confirmed using the standard addition method. The proposed procedures were successfully applied to the determination of cetirizine in bulk and tablet form, with high percentage of recovery, good accuracy and precision.

Extraction-spectrophotometric determination of phenytoin in capsules and plasma using potassium permanganate/dicyclohexano-24-crown-8.

An extraction-spectrophotometric method for the determination of phenytoin in capsules and plasma is presented. The method is based upon oxidation of phenytoin using alkaline potassium permanganate solubilized in chloroform/cyclohexane (1:1) after crowning with dicyclohexano-24-crown-8 (DC-24-C-8). The formed benzophenone being soluble in the oxidation reaction medium was directly measured at 238 nm. The optimum conditions for the reaction were studied and the detection limit was found to equal 1.2 mg/100 ml. The developed method was applied to the determination of the drug in capsules and plasma. The method is simple, accurate and avoids laborious multistep extraction procedures.

Spectrophotometric determination of acrivastine in urine and capsules.

Three sensitive and accurate spectrophotometric methods are presented for the determination of the antihistaminic acrivastine (ACR) in capsules and urine. The first method utilizes the reaction of 2-nitrophenylhydrazine hydrochloride in presence of dicyclohexylcarbodiimide and pyridine. The violet colour of the resulting acid hydrazide is measured at 550 nm. The second method is based on alkaline oxidation of the drug with potassium permanganate and subsequent measurement of the formed manganate ion at 608 nm. The third method uses derivative spectrophotometry for the determination of ACR. The last method is extended to the in vitro determination of the drug in urine. All methods gave a relative standard deviation of less than 2%.

Assay for amoxycillin in urine using derivative spectrophotometry.

Three derivatives spectrophotometric methods have been described for the assay of amoxycillin in urine. The methods were based on the amplitude measurements of second derivative (D2), first derivative difference (delta D1) or second derivative difference (delta D2) curves. These values were linearly correlated to the amoxycillin concentration in the range of 0.2-1.0 mg% with negligible intercepts. The absolute recovery from urine specimens was found to be 98%. The within-day and between-day precision were satisfactory.

Spectrophotometric determination of cimetidine in the presence of its acid-induced degradation products.

Cimetidine has been determined in the presence of its acid-induced degradation products using a second derivative (D2-) spectrophotometric method (method I) or a colorimetric method (method II). The former is based on D2-value measurement at 216 nm, whilst the latter depends on charge-transfer complexation with dichlorophenol-indophenol. The two methods are proved to be stability indicating, since plots of log C% versus time were linear. The application to cimetidine determination in tablets and ampoules gave good results.

Computer-assisted spectrophotometry: multicomponent analysis with a discrete fourier transform.

A computer-assisted method for analysis of multicomponent mixtures by use of conventional absorbance as well as discrete Fourier transforin coefficients (combined trigonometric functions) is presented. The program can store absorbance data (A vs. lambda), process data by convolution with combined trigonometric functions, apply least-squares analysis and solve the resultant simultaneous linear equations, and display data on screen, printer or plotter.

Determination of chlorpheniramine maleate, dihydrocodeine bitartrate and ephedrine hydrochloride in cough mixture by derivative and differential spectrometry.

A method is presented for the determination of chlorpheniramine maleate, dihydrocodeine bitartrate and ephedrine hydrochloride in a three-component mixture without prior separation. Chlorpheniramine maleate was determined by the first and second derivative-differential spectrophotometry, while dihydrocodeine bitartrate was directly determined using first and second derivative measurements. Ephedrine hydrochloride could be determined by first and second derivative spectrophotometry after its oxidation with sodium metaperiodate. The method was proved using synthetic mixtures of these drugs and was applied for their determination in syrup with a coefficient of variation less than 2%.

Colorimetric determination of some penicillins and cephalosporins with 2-nitrophenylhydrazine hydrochloride.

A simple and sensitive calorimetric method for the determination of some penicillins and cephalosporins is presented. The method is based on reaction with 2-nitrophenylhydrazine hydrochloride in presence of dicyclohexylcarbodi-imide and pyridine. The violet colour of the resulting acid hydrazide is measured at the appropriate wavelength. The method has been applied to determination of these antibiotics in bulk and dosage forms, with a coefficient of variation less than 2%.

Derivative spectrophotometric determination of clotrimazole in single formulations and in combination with other drugs.

First (D1) and second (D2) derivative spectrophotometric methods are presented for the determination of clotrimazole after its acid hydrolysis. Mixtures of clotrimazole with azidamfenicol and dexamethasone have been assayed using D2 measurement at 302 nm after acid hydrolysis for clotrimazole, D1 measurement at 288 nm for azidamfenicol, and D1 measurement at 436 nm after reaction with phenylhydrazinium sulfate for dexamethasone. Reproducible results with relative standard deviations of less than 2% are obtained. The proposed method has been successfully applied to the analysis of creams, topical solutions, and vaginal tablets.

Spectrophotometric determination of some 1,4-benzodiazepines by use of orthogonal polynomials.

A direct spectrophotometric method for the determination of some 1,4-benzodiazepines, namely, nitrazepam, prazepam and dipotassium chlorazepate, in the presence of their degradation products, is presented. The method depends upon the use of orthogonal polynomials, to eliminate interferences by degradation products to the absorption spectra of the intact drugs. The method was proved using synthetic mixtures of the intact drugs with their respective degradation products and its suitability to monitor for the stability of the drugs was demonstrated. The method has been applied to the determination of these drugs in dosage forms, with a coefficient of variation less than 2%.

Derivative spectrophotometric determination of some corticosteroids in combinations with other drugs.

Three 2-component mixtures, namely, dexamethazone-chlorpheniramine maleate, prednisolone-chlorpheniramine maleate, and prednisolone-salicylic acid, have been assayed using their first (D1) and second (D2) derivative spectra in methanol, delta absorption (delta A), and second derivative of delta A (delta D2) spectra in methanol-methanolic HCl. In the first 2 mixtures, chlorpheniramine maleate was determined by measuring its delta D2 value at 278 nm, while dexamethazone and prednisolone were analyzed by measuring their D1 values at 248 nm. Prednisolone and salicylic acid were analyzed in combination by using their respective D2 spectral responses at 272 and 314 nm. The results obtained are reasonably reproducible with a relative standard deviation less than 2%. The method has been successfully applied to the analysis of these drugs in their pharmaceutical formulations.

Second derivative spectrophotometric determination of acetaminophen and phenacetin in presence of their degradation products.

A rapid and accurate method for determining acetaminophen and phenacetin in presence of their degradation products is presented. Solutions of these drugs in 0.1N HCl were analyzed by measuring their second derivative spectral response at 295 nm where the degradation products do not interfere. The mean percent recoveries for mixtures of acetaminophen and/or phenacetin with the corresponding degradation products were 100.2 +/- 0.6 and 100.6 +/- 1.1, respectively. The method can be used for assessing the stability of the 2 drugs. The proposed method is also applied to the determination of acetaminophen in tablets and syrups.

A sensitive colorimetric method for the determination of imipramine hydrochloride and desipramine hydrochloride.

A simple and rapid colorimetric method for the determination of imipramine hydrochloride and desipramine hydrochloride in their tablet formulations and in biological fluids is presented. The method is based on the reaction of these drugs with 3-methyl-2-benzothiazolone hydrazone in the presence of ferric chloride, with direct measurement at 635 nm. Cyclohexane was used to extract these drugs from serum and urine, at basic pH, by a single manual extraction. The method can detect 0.5 microgram/ml of each drug. The main advantages of this method are its simplicity and high sensitivity.

Determination of ethinyloestradiol in the presence of norethisterone by derivative-difference spectrophotometry.

A simple and direct method for the determination of ethinyloestradiol as a minor component in the presence of norethisterone and in oral contraceptive tablets is presented. The method is based on measuring the signal intensity, d delta A/d lambda and d2 delta A/d lambda 2, of the generated first and second derivative spectra of the delta-absorbance curves obtained by measuring solutions in methanol and methanol-sodium hydroxide at certain wavelengths. The method has been applied to the determination of ethinyloestradiol in oral contraceptive tablets, with a coefficient of variation of less than 2%.