Heba Elmansi

Spectrofluorimetric Determination of Paroxetine HCl in Pharmaceuticals via Derivatization with 4-chloro-7- nitrobenzo-2-oxa-1,3-diazole (NBD-Cl)

A sensitive and simple spectrofluorimetric method has been developed and validated for the determination of the antidepressant paroxetine HCl (PXT) in its dosage forms. The method was based on coupling reaction of PXT with 4-chloro-7-nitrobenzo-2- oxa-1,3-diazole (NBD-Cl) in an alkaline medium (pH 8) to form a highly fluorescent derivative that was measured at 530 nm after excitation at 460 nm. The factors affecting the formation and stability of the reaction product were carefully studied and optimized. The fluorescence–concentration plot is rectilinear over the range 0.2-6 μg/mL with LOD of 0.08 μg/mL and LOQ of 0.24 μg/mL respectively. The method was applied to the analysis of commercial tablets and the results were in good agreement with those obtained using the reference method. The mean percentage recoveries for paxetin and xandol tablets were 101.27 ± 1.79 and 101.33 ± 1.19 respectively. A proposal of the reaction pathway was postulated.

Development and validation of stability indicating method for determination of sertraline following ICH guidlines and its determination in pharmaceuticals and biological fluids

BackgroundSertraline is a well known antidepressant drug which belongs to a class called selective serotonin reuptake inhibitor. Most published methods do not enable studying the stability of this drug in different stress conditions.ResultsTwo new methods were developed for the determination of sertraline (SER). Both methods are based on coupling with 4-chloro-7-nitrobenzo-2-oxa-1,3-diazole (NBD-Cl) in borate buffer of pH 7.8 and measuring the reaction product spectrophotometrically at 395 nm (Method I) or spectrofluorimetrically at 530 nm upon excitation at 480 nm (Method II). The response-concentration plots were rectilinear over the range 2-24 μg/mL and 0.25-5 μg/mL for methods I and II respectively with LOD of 0.18 μg/mL and 0.07 μg/mL, and LOQ of 0.56 μg/mL and 0.21 μg/mL for methods I and II, respectively.ConclusionBoth methods were applied to the analysis of commercial tablets and the results were in good agreement with those obtained using a reference method. The fluorimetric method was further applied to the in vivo determination of SER in human plasma. A proposal of the reaction pathway was presented. The spectrophotometric method was extended to stability study of SER. The drug was exposed to alkaline, acidic, oxidative and photolytic degradation according to ICH guidelines. Moreover, the method was utilized to investigate the kinetics of oxidative degradation of the drug. The apparent first order rate constant and t1/2 of the degradation reaction were determined.

Derivative Spectrophotometric and Liquid Chromatographic Methods for the Simultaneous Determination of Metoclopramide Hydrochloride and Aspirin in Pharmaceuticals

Two simple analytical methods were developed and validated for the analysis of a binary mixture of metoclopramide (MET) and aspirin (ASP). The first method depends on measuring the first derivative amplitudes at 257 nm for MET and at 310 nm for ASP, respectively. The calibration graphs were linear in the range of 0.25-20.0 µg/mL for MET and 10.0-200.0 µg/mL for ASP. For the second method, good chromatographic separation was achieved using Promosil C18 column (250 × 4.6 mm i.d., 5 µm particle size). Mobile phase consisting of methanol and 0.02 M phosphate buffer in the ratio of 60:40 (v/v) at pH 4.0 was pumped at a flow rate of 1 mL/min with UV detection at 260 nm. Indapamide was used as an internal standard. The method showed good linearity over the concentration ranges of 0.20-10.0 and 10.0-200.0 μg/mL with limits of detection of 0.06, 1.81 μg/mL and limits of quantification of 0.17, 5.46 μg/mL for MET and ASP, respectively. The results of the proposed methods were statistically compared with those obtained by the official United States Pharmacopeia method revealing non-significant differences in the performance of the methods regarding accuracy and precision. The suggested methods were successfully applied for the simultaneous analysis of the studied drugs in their co-formulated tablets as well as in their single dosage forms.

Determination of Two Ternary Mixtures for Migraine Treatment Using HPLC Method with Ultra Violet Detection

New, selective, and accurate HPLC methods are described for the analysis of two ternary mixtures used for migraine treatment containing drotaverine hydrochloride (DRT) with caffeine (CAF), and dipyrone (DIP) (mixture I), or paracetamol (PAR) (mixture II). The described methods used a mobile phase consisting of methanol: 0.02 M sodium dihydrogen phosphate in two different ratios. The pH of the mobile phases was adjusted to 4 and UV detection at 220 nm was used. Good chromatographic separations were achieved using Promosil C18 column. Spironolactone (SPL) and propranolol (PRP) were used as internal standards (ISs) for mix. I and II, respectively.

Highly sensitive spectrofluorimetric method for the determination of two antimigraine drugs in their tablets and in biological fluids. Application to content uniformity testing

A highly sensitive and simple spectrofluorimetric method has been developed for the determination of almotriptan malate (ALM) and zolmitriptan (ZOL) in their pharmaceutical preparations. The proposed method is based on the investigation of the fluorescence spectral behavior of the two drugs in aqueous acidic systems. The fluorescence intensity was measured at 360 and 350 nm after excitation at 270 nm for ALM and ZOL, respectively. The fluorescence–concentration plots were rectilinear over the range 0.1–1.2 μg mL−1 and 5–40 ng mL−1, with lower detection limits of 0.03 μg mL−1 and 0.70 ng mL−1 for ALM and ZOL, respectively. The proposed method was successfully applied for the assay of commercial tablets as well as for content uniformity testing. The application of the proposed method was extended to the assay of ZOL in biological fluids. The results were statistically compared to those obtained by comparison methods and were found to be in good agreement.

Determination of Oxybutynin in Pharmaceuticals via Reaction with Mixed Acids Anhydrides: Application to Content Uniformity Testing

Sensitive and simple spectrophotometric (Method I) and spectrofluorimetric (Method II) methods were developed and validated for the determination of oxybutynin HCl (OXB) in its dosage forms. The method was based on the reaction of OXB with malonic acid anhydride in acetic acid anhydride to form a highly yellow colored product that was measured at 375 nm spectrophotometrically. The same reaction product exihibits strong fluorescence that was measured at 440 nm after excitation at 390 nm. The factors affecting formation and stability of the reaction product were carefully studied and optimized, and the reaction mechanism was postulated. The absorbance-concentration plot is rectilinear over the range 4–40 μg/mL with LOD of 1.12 μg/mL and LOQ of 3.39 μg/mL. The fluorescence-concentration plot is rectilinear over the range 0.5–6 μg/mL with LOD of 0.11 μg/mL and LOQ of 0.33 μg/mL. The method was applied to the analysis of commercial tablets Detronin® and Uripan®. Statistical comparison of the results with those of the reference method revealed good agreement and proved that there were no significant difference in the accuracy and precision between the two methods respectively. The study was extended to content uniformity testing.

Simultaneous HPLC Determination of Cisatracurium and Propofol in Human Plasma via Fluorometric Detection

The proposed method describes a high performance liquid chromatographic method with fluoremetric detection for the determination of cisatracurium (CIS) and propofol (PRP) simultaneously, which are co-administered as a pre-operative injection mixture. The separation of the two drugs was achieved using monolithic column (100 mm and 4.6 mm internal diameter) and mixture of methanol and 0.1 M phosphate buffer in the ratio of 80:20 (v/v) at pH 4.5 as a mobile phase. The fluorescence detection was carried out at 230/324 nm. The procedure showed good linearity through the concentration ranges of 0.01-1.00 μg/mL and 0.1-3.0 μg/mL with limits of detection of 0.002, 0.030 μg/mL and limits of quantification of 0.006, 0.100 μg/mL for CIS and PRP, respectively. Simultaneous determination of CIS and PRP in spiked human plasma samples was additionally executed and the results were satisfactory precise and accurate.

Stability indicating HPLC Method Coupled with Fluorescence Detection for the Determination of Cyproheptadine Hydro-chloride in Its Tablets. Studies on Degradation Kinetics

Abstract A sensitive, simple and rapid stability-indicating HPLC method using fluorescence detection was developed for the quantitative determination of the antihistaminic drug cyproheptadine hydrochloride (CYP). Good chromatographic separation was achieved using Shimadzu VP-ODS column (150 mm x 4.6 mm i.d., 5 μm particle size) and fluorescence detection at 410 nm after excitation 280 nm. Mobile phase consisting of methanol and 0.02 M phosphate buffer in the ratio of 65:35, v/v at pH 4.5 was pumped at a flow rate of 1 mL/min. Xipamide (XIP) was used as an internal standard (IS). The method was successfully applied to the analysis of CYP in its commercial tablets and the results were in good agreement with those obtained with the official USP method. The application of the proposed method was extended to stability studies of CYP after exposure to different ICH recommended stress conditions, such as acidic, alkaline, oxidative and photolytic degradation. Moreover, the method was utilized to investigate the kinetics of the oxidative degradation of CYP. The apparent first-order rate constant, half-life time, and activation energies of the degradation process were calculated. A proposal for the degradation pathway was presented.