Xipamide Research Articles

Univariate versus multivariate spectrophotometric data analysis of triamterene and xipamide; a quantitative and qualitative greenly profiled comparative study

Triamterene (TRI) and xipamide (XIP) mixture is used as a binary medication of antihypertension which is considered as a major cause of premature death worldwide. The purpose of this research is the quantitative and qualitative analysis of this binary mixture by green univariate and multivariate spectrophotometric methods. Univariate methods were zero order absorption spectra method (D0) and Fourier self-deconvolution (FSD), as TRI was directly determined by D0 at 367.0 nm in the range (2.00–10.00 µg/mL), where XIP show no interference. While XIP was determined by FSD at 261.0 nm in the range (2.00–8.00 µg/mL), where TRI show zero crossing. Multivariate methods were Partial Least Squares, Principal Component Regression, Artificial Neural Networks, and Multivariate Curve Resolution-Alternating Least Squares. A training set of 25 mixtures with different quantities of the tested components was used to construct and evaluate them, 3 latent variables were displayed using an experimental design. A set of 18 synthetic mixtures with concentrations ranging from (3.00–7.00 µg/mL) for TRI and (2.00–6.00 µg/mL) for XIP, were used to construct the calibration models. A collection of seven synthetic mixtures with various quantities was applied to build the validation models. All the proposed approaches quantitative analyses were evaluated using recoveries as a percentage, root mean square error of prediction, and standard error of prediction. Strong multivariate statistical tools were presented by these models, and they were used to analyze the combined dosage form available on the Egyptian market. The proposed techniques were evaluated in accordance with ICH recommendations, where they are capable of overcoming challenges including spectral overlaps and collinearity. When the suggested approaches and the published one were statistically compared, there was no discernible difference between them. The green analytical method index and eco-scale tools were applied for assessment of the established models greenness. The suggested techniques can be used in product testing laboratories for standard pharmaceutical analysis of the substances being studied.

An eco-friendly micellar HPLC method for the simultaneous determination of triamterene and xipamide in active pharmaceutical ingredients and marketed tablet dosage form

AbstractIn the last few years, the use of surfactants as mobile phase additives in reversed phase liquid chromatography (RPLC) has been steadily developing and improving. Surfactants modify the polarity of the stationary phase which in turn decreases the amount of organic solvent required for elution of the analytes rendering the methodologies linked to them greener and more eco-friendly. Brij-35 is a fatty alcohol ethoxylates non ionic surfactant, which is less widely used as mobile phase additive. Brij-35 can decrease stationary phase polarity while remaining neutral. In this research, Brij-35 was studied in the separation and determination of marketed antihypertensive combination therapy composed of triamterene (TRM) and xipamide (XIP). TRM and XIP are diuretics used for treatment of essential hypertension and associated edema conditions. Chromatographic separation was achieved on RP-C18 column (Kinetix®, 5 µm, 15 cm × 4.6 mm) at flow rate 1 mL min−1 and UV-detection at 254 nm. Isocratic elution was performed using mobile phase composed of 0.1 M Brij-35: methanol (MeOH) (60:40, v/v). The analytes were well separated and quantified within linearity ranges of 5–50 µg mL−1 for both drugs in short retention time (2.6 and 5.3 min. for TRM and XIP, respectively). Since claiming greenness is not enough, Green Analytical Procedure Index (GAPI) was used to demonstrate the superiority of the proposed method over the previously reported methods. GAPI is a new metric for evaluation of the ecological impact of analytical procedures. The proposed method was validated according to ICH guidelines and applied successfully for simultaneous determination of the drugs in their co-formulated tablets.

Validated capillary zone electrophoretic method for simultaneous analysis of benazepril in combination with amlodipine besylate and hydrochlorothiazide

In this work, a novel, simple, and quick capillary zone electrophoresis (CZE) method was proposed for simultaneous analysis of benazepril (BEN) with other co-administrated antihypertensive drugs, amlodipine besylate (AML) and hydrochlorothiazide (HCT), using a diode array detector (DAD). A fused silica capillary (78.5 cm total length, 70 cm effective length, and 75 μm id) was used in separation using a 40 mM phosphate buffer pH 7.5 as a running background electrolyte (BGE) under a positive potential of 30 KV, at a stable temperature of 25 °C for capillary during separation. Hydrodynamic injections were performed for 12 s at 50 mbar, and detection was performed at 210 nm for AML and BEN, at 225 nm for HCT, and at 232 nm for xipamide (XIP) added as an internal standard (IS). Separation of the three analyzed drugs and the IS was performed in less than 8 min. Migration times were 4.06, 5.23, 6.69, and 7.3 min for AML, HCT, BEN, and XIP, respectively. The findings proved that the proposed method was linear in the range of 10–80 μg/mL for all drugs with correlation coefficients >0.9994. The limit of detection (LOD) values of AML, HCT, and BEN were 1.004, 1.224, and 0.896 μg/mL, respectively, whereas the limit of quantification (LOQ) values were 3.124, 3.727, and 2.749 μg/mL for the cited drugs, respectively. Peak identity and purity were confirmed by DAD. The developed CZE method was applied for the analysis of the three antihypertensive drugs successfully in their combined pharmaceutical tablets, and it can be used for the quality control of single-pill combination (SPC) samples of these drugs in short time.

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

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.

Physicochemical and Biological Studies on Xipamide and Some of Its Complexes

The new complexes of xipamide (XPD) with Ti(III), Ni(II), Pd(II), Zr(IV), Ce(IV), and U(VI) have been synthesized. Elemental analysis, magnetic properties, molar conductivities, thermal analysis, and UV-Vis, IR and 1H NMR spectra, elucidated the structures of complexes. According to spectral data, xipamide behaved in the obtained complexes as a bidentate chelating anion with the charge (–1) and coordinated via oxygen atoms of the deprotonated phenolic and carbonyl groups. Kinetic parameters of thermogravimetric analysys and its differential have been evaluated by using the Coats–Redfern and Horowitz–Metzeger methods. Thermodynamic data indicated thermal stability of all complexes. The ligand and its metal complexes were screened for their antifungal activity against A. fumigatus,G. candidum, syncephalastrum, and C. albicans, and antibacterial activities against two Gram-positive bacteria species, such as S. aureus and B. subtilis, two Gramnegative such as E. coli and P. aeruginosa.

Two liquid chromatographic approaches for the simultaneous determination of xipamide and its degradation product (2,6-xylidine) using time-programmed fluorescence detection.

A study of the performance of reversed-phase chromatography with a programmable multiwavelength fluorimetric technique using either conventional hydro-organic or micellar eluent is established for the determination of xipamide (XIP) in the presence of its degradation product, 2,6-xylidine (XY). In conventional liquid chromatography (CLC), the analyses were carried out on a Promosil ODS 100Å column (250mm×4.6mm i.d., 5μm) using a mobile phase consisting of methanol/0.1M phosphate buffer (65: 35, v/v) at pH4.0. For micellar liquid chromatography (MLC), a short Spherisorb column (150mm×4.6mm i.d., 5μm) was employed in conjunction with a greener mobile phase (pH5.0) containing 0.1M sodium dodecyl sulfate and 15% n-propanol. CLC proved to be superior to MLC in terms of sensitivity for the determination of the degradation product because it could detect trace amounts down to 10.0ng/ml of XY as a degradation product in XIP. However, MLC represents an eco-friendly approach for the simultaneous determination of XIP and XY. In addition, the opportunity for the direct introduction of biological matrices into the chromatographic system is one of the distinctive benefits of MLC. The proposed methods were applied for the determination of XIP in its tablets, human urine and content uniformity testing. The results of the proposed methods were statistically compared with those obtained using the comparison fluorimetric method, revealing no significant differences in the performance of the methods regarding accuracy and precision.

Stability-indicating HPLC-DAD method development, validation, and stress degradation studies for triamterene and xipamide in their combined tablet dosage form

A simple stability-indicating high-performance liquid chromatography-diode array detection (HPLC-DAD) method has been developed for the simultaneous determination of triamterene (TRI) and xipamide (XIP) in presence of the degradation products generated in studies of forced decomposition. Drugs were subjected to stress by hydrolysis (acidic, alkaline, and neutral), oxidation, photolysis (254 and 365 nm), and dry and wet heat treatments. Degradation occurs under acidic and alkaline conditions (TRI only), oxidative stress (TRI and XIP), and by photolysis (XIP only), but both drugs were stable under other stress conditions investigated. Separation of the two drugs from all the degradant peaks was achieved within 11 min using C8 column (250 × 4.6 mm, 5 μm) and mobile phase consisting of acetonitrile and 0.05 M phosphate buffer adjusted to pH 4 delivered at a flow rate of 1 mL min−1 using gradient elution system. The drugs were quantified at 220 nm using photodiode array detector, based on peak area. Peak homog...

High performance liquid chromatography for simultaneous determination of xipamide, triamterene and hydrochlorothiazide in bulk drug samples and dosage forms.

A novel, simple and robust high-performance liquid chromatography (HPLC) method was developed and validated for simultaneous determination of xipamide (XIP), triamterene (TRI) and hydrochlorothiazide (HCT) in their bulk powders and dosage forms. Chromatographic separation was carried out in less than two minutes. The separation was performed on a RP C-18 stationary phase with an isocratic elution system consisting of 0.03 mol L(-1) orthophosphoric acid (pH 2.3) and acetonitrile (ACN) as the mobile phase in the ratio of 50:50, at 2.0 mL min(-1) flow rate at room temperature. Detection was performed at 220 nm. Validation was performed concerning system suitability, limits of detection and quantitation, accuracy, precision, linearity and robustness. Calibration curves were rectilinear over the range of 0.195-100 μg mL(-1) for all the drugs studied. Recovery values were 99.9, 99.6 and 99.0 % for XIP, TRI and HCT, respectively. The method was applied to simultaneous determination of the studied analytes in their pharmaceutical dosage forms.

Stability–Indicating Spectrofluorimetric Methods for the Determination of Metolazone and Xipamide in Their Tablets. Application to Content Uniformity Testing

A highly sensitive, simple and rapid stability-indicating spectrofluorimetric method was developed for the determination of metolazone (MET) and xipamide (XPM) in their tablets. The proposed method is based on the measurement of the native fluorescence of MET in methanol at 437nm after excitation at 238nm and XPM in alkaline methanolic solution at 400nm after excitation at 255nm. The fluorescence-concentration plots were rectilinear over the range of 2.0- 20.0ng/mL for MET and 0.2- 2.0μg/mL for XPM, with lower detection limits (LOD) of 0.35ng/mL and 0.02μg/mL and a lower quantification limit (LOQ) of 1.05ng/mL and 0.07μg/mL for MET and XPM, respectively. The method was successfully applied to the analysis of MET and XPM in their commercial tablets and the results were in good agreement with those obtained using the official and comparison methods, respectively. Furthermore, content uniformity testing of the studied pharmaceutical tablets was also conducted. The application of the proposed method was extended to stability studies of MET and XPM after exposure to different forced degradation conditions, such as acidic, alkaline, oxidative and photolytic degradation conditions, according to ICH Guidelines. Moreover, the method was utilized to investigate the kinetics of the alkaline, acidic and photolytic degradation of MET. The apparent first-order rate constants and half-life times were calculated. Proposals for the degradation pathways for both MET and XPM were postulated.

Simultaneous determination of metolazone and spironolactone in raw materials, combined tablets and human urine by high performance liquid chromatography

A new, specific and sensitive reversed-phase high performance liquid chromatographic method was developed for the simultaneous determination of two diuretic drugs; metolazone (MET) and spironolactone (SPL). Good chromatographic separation was achieved within 5.0 min on 150 mm × 4.6 mm i.d., 5 μm particle size Spherisorb-ODS 2 C18 column. A mobile phase containing a mixture of methanol and 0.02 M phosphate buffer (70 : 30) v/v at pH 3.0 was used. The analysis was performed at a flow rate of 1 mL min−1 with UV detection at 235 nm. Xipamide (XPM) was used as an internal standard (IS). The proposed method was rectilinear over the ranges of 0.05–1.0 μg mL−1 and 0.5–10.0 μg mL−1 with limits of detection (LOD) of 0.009, 0.04 ng mL−1 and limits of quantification (LOQ) of 0.03, 0.11 μg mL−1 for MET and SPL, respectively. The suggested method was successfully applied for the simultaneous analysis of the studied drugs in their laboratory prepared mixtures, single tablets and co-formulated tablets. The method was further extended to the determination of both drugs in spiked human urine. The mean percentage recoveries of MET and SPL in spiked human urine were 99.33 ± 2.37 and 99.72 ± 3.27, respectively. The proposed method was also applied for the determination of the studied drugs in the presence of some co-administered or co-formulated drugs without any interference. Statistical evaluation and comparison of the data obtained by the proposed and comparison methods revealed no significant difference between the two methods regarding accuracy and precision.

Bioavailability study of triamterene and xipamide using urinary pharmacokinetic data following single oral dose of each drug or their combination

An efficient chromatographic method for the simultaneous determination of triamterene (TRI) and xipamide (XIP) in urine samples, based on high performance liquid chromatography with photodiode array detector (HPLC–DAD) has been developed. The HPLC separation was performed on a RP stainless-steel C-18 analytical column (250 mm × 4.6 mm, 5 μm) with a gradient elution system of 0.05 M phosphate buffer adjusted to pH 4.0 and methanol as the mobile phase. The method was used to determine the urinary excretion profile and to calculate different urinary pharmacokinetic parameters following oral dose of their combination compared with single oral doses of each drug and hence comparing their bioavailability. Quantitation was performed using chlorthalidone as internal standard. The calibration graphs of each drug were rectilinear in the range of 0.2–40 μg/mL urine for TRI and 0.2–15 μg/mL urine for XIP. An HPLC–DAD method was also successfully developed for the simultaneous determination of the investigated drugs in pharmaceutical preparations. The methods were validated in terms of linearity, accuracy, precision, selectivity, limits of detection and quantitation and other aspects of analytical validation.

Spectrophotometric and spectrodensitometric determination of triamterene and xipamide in pure form and in pharmaceutical formulation

Sensitive and validated UV-spectrophotometric, chemometric and TLC-densitometric methods were developed for determination of triamterene (TRM) and xipamide (XIP) in their binary mixture, formulated for use as a diuretic, without previous separation. Method A is the isoabsorptive point spectrophotometry, in which TRM concentration alone can be determined at its λ(max) while XIP concentration can be determined by measuring total concentration of TRM and XIP at their isoabsorptive point followed by subtraction. Method B is the ratio subtraction spectrophotometry, where XIP can be determined by dividing the spectrum of the mixture by the spectrum of TRM (as a divisor) followed by subtracting the constant absorbance value of the plateau region, then finally multiplying the produced spectrum by the spectrum of the divisor, while TRM concentration can be determined at its λ(max). Method C is a chemometric-assisted spectrophotometry where classical least squares, principal component regression, and partial least squares were applied. Method D is a TLC-densitometry; this method depends on quantitative densitometric separation of thin layer chromatogram of TRM and XIP using silica gel plates at 254 nm. The proposed methods were successfully applied for the analysis of TRM and XIP in their pharmaceutical formulation and the results were statistically compared with the established HPLC method.

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Xipamide is a safe and effective antihypertensive in Blacks

Xipamide is a safe and effective antihypertensive in Blacks

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Xipamide, indapamide and hypokalaemia

Xipamide, indapamide and hypokalaemia

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XIP AMIDE PHARMACOKINETICS

XIP AMIDE PHARMACOKINETICS