Ramipril Research Articles

Ramipril can alleviate the accumulation of renal mesangial matrix in rats with diabetic nephropathy by inhibiting insulin-like growth factor-1.

Purpose To investigate the impact of Ramipril (RAM) on the expressions of insulin-like growth factor-1 (IGF-1) and renal mesangial matrix (RMM) in rats with diabetic nephropathy (DN). Methods The Sprague Dawley rats were divided into normal control (NC) group (n = 12), DN group (n = 11), and DN+RAM group (n = 12). The ratio of renal weight to body weight (RBT), fasting blood glucose (FBG), HbA1c, 24-h urine protein (TPU), blood urea nitrogen (BUN), creatinine (Cr), renal pathological changes, the levels of IGF-1, fibronectin (FN), type IV collagen (Col-IV), and matrix metalloproteinases (MMP)-2 were compared among the groups. Results Compared with NC group, the RBT, FBG, HbA1c, TPU, BUN, Cr, and RMM in DN group were significantly increased (P < 0.05), the IGF-1, FN, and Col-IV were significantly upregulated (P < 0.05), while MMP was significantly downregulated (P < 0.05). Compared with DN group, the indexes except for the FBG and HbA1c in DN+RAM group were significantly improved (P < 0.05), among which IGF-1 exhibited significant positive correlation with TPU(r=0.937), FN(r=0.896) and Col-IV(r=0.871), while significant negative correlation with MMP-2 (r=-0.826) (P<0.05). Conclusion RAM may protect the kidneys by suppressing IGF-1 and mitigating the accumulation of RMM.

How to Treat Hypertension in Venlafaxine-Medicated Patients-Pharmacokinetic Considerations in Prescribing Amlodipine and Ramipril.

Amlodipine (AMLO) and ramipril (RAMI) belong to the most prescribed drugs in patients with hypertension, a condition also encountered in depression. Venlafaxine may worsen hypertension because of noradrenergic properties. Although of special clinical relevance, data on pharmacokinetic interactions between AMLO, RAMI, and venlafaxine (VEN) are lacking. Two TDM databases consisting of plasma concentrations of VEN and its active metabolite O-desmethylvenlafaxine (ODVEN) were analyzed. We considered a group of patients comedicated with AMLO, VAMLO (n = 22); a group comedicated with RAMI, VRAMI (n = 20); and a 4:1 control group age matched to the VAMLO group receiving VEN without confounding medications, V0 (n = 88). Plasma concentrations of VEN, ODVEN, and active moiety, AM (VEN + ODVEN); metabolic ratio (ODVEN/VEN); and dose-adjusted plasma concentrations (C/D) were compared using nonparametric tests. Groups did not differ in daily VEN dose, age, or sex. The metabolic ratio (ODVEN/VEN) was lower in the AMLO group (P = 0.029), whereas the RAMI group showed lower values for ODVEN (P = 0.029). All other parameters showed no significant differences. Significantly lower values for the metabolic ratio in the AMLO group are unlikely to be explained by cytochrome P450 (CYP) 3A4 and weak CYP2D6 inhibition by AMLO. Other factors such as differences in CYP2D6 polymorphisms and metabolizer status may better explain the findings. Ramipril showed modest effects with changes in ODVEN concentrations that did not remain significant after dose-adjusted comparisons.

VERSATILE RP-HPLC METHOD DEVELOPMENT FOR QUANTITATIVE ESTIMATION OF TELMISARTAN AND RAMIPRIL IN ANIMAL PLASMA

Objective: A fast, specific, and sensitive high-performance liquid chromatographic method has been developed and validated for the quantitative determination of unchanged Ramipril (RAM) and Telmisartan (TEL) in animal plasma.Methods: Analytes were extracted from animal plasma, 250 µl of animal plasma sample were mixed with internal working standard (25 ngmL-1) with the further addition of chloroform (HPLC Grade, Merck). The clear organic layer was separated and reconstituted to 1 ml in mobile phase and analysed by HPLC. The method was validated and evaluated in terms of linearity, accuracy, precision, specificity, limit of detection and limit of quantitation.Results: Absorption maxima of TEL and RAM was found to be 270 and 273 nm respectively. TEL and RAM with their respective internal standards (I. S.) were found to be well separated from the co-eluted components and there were no interferences from the endogenous material. The limit of detection (LOD) and limit of quantitation (LOQ) were found to be 2.01±.05; 4.88±0.10 and 0.11 and 0.25 for TEL and RAM respectively on the basis of a signal to noise ratio. The ruggedness of the method at various parameters was found to be±1.94% and±1.02% for TEL and RAM respectively. The low values of %RSD (&lt;2.0) for each of the drug proposed that during all deliberate variations, middle-quality control (MQC) was not affected and it was in accordance with that of actual.Conclusion: Thus developed High-Performance Liquid Chromatography (HPLC) method was found to be more accurate, precise, sensitive, selective and reproducible.

3 przypadki pacjentów, u których warto stosować ramipryl

3 przypadki pacjentów, u których warto stosować ramipryl

Ramipryl z amlodypiną – klasycznie, wciąż skutecznie

Ramipryl z amlodypiną – klasycznie, wciąż skutecznie

Ultrasound assisted dispersive liquid-liquid microextraction coupled with high performance liquid chromatography designated for bioavailability studies of felodipine combinations in rat plasma.

Felodipine (FLD), a calcium channel antagonist, is commonly prescribed for the treatment of hypertension either with Metoprolol (MET) or Ramipril (RAM) in two different drug combinations. FLD has high plasma protein binding ability affecting its extraction recoveries from plasma samples. Hence, a specific ultrasound assisted dispersive liquid-liquid microextraction (UA-DLLME) method coupled with HPLC using photodiode array detector was developed and validated for the simultaneous determination of FLD, MET and RAM in rat plasma after oral administration of these combinations. The factors affecting UA-DLLME were carefully optimized. In this study, UA-DLLME method could provide simple and efficient plasma extraction procedures with superior recovery results. Under optimum condition, all target drugs were separated within 13min. The validation procedures was carried out in agreement with US-FDA guidelines and shown to be suitable for anticipated purposes. Linear calibration ranges were obtained in the range 0.05-2.0μgmL-1 for FLD and MET and 0.1-2.0μgmL-1 for RAM with detection limits of 0.013-0.031μgmL-1 for all the studied drug combinations. The%RSD for inter-day and intra-day precisions was in range of 0.63-3.85% and the accuracy results were in the range of 92.13-100.5%. The validated UA-DLLME-HPLC method was successfully applied for the bioavailability studies of FLD, MET and RAM. The pharmacokinetic parameters were calculated for all the investigated drugs in rats after single-dose administrations of two different drug combinations. Although FLD was bioequivalent in the two formulations, a small increase in plasma levels of MET and RAM was found in the presence of FLD.

The Performance of Boron‐Doped Diamond Electrode for the Determination of Ramipril and its Association with Hydrochlorothiazide

AbstractThe voltammetric behavior of ramipril (RMP), an angiotensin‐converting enzyme inhibitor, was investigated for the first time in the literature on a boron‐doped diamond electrode (BDDE) using cyclic (CV) and square‐wave voltammetry (SWV). Its behavior was also considered in the presence of a thiazide diuretic, hydrochlorothiazide (HCTZ), for the simultaneous determination. The performance of BDDE and glassy carbon electrode (GCE) was compared, since RMP provides a high oxidation potential. It was observed that the anodic peak potentials for HCTZ and RMP at the BDDE were 1.23 and 1.67 V (vs. Ag/AgCl (3.0 mol L‐1 KCl)) by CV in BR buffer solution (pH 2.0), respectively. The influence of supporting electrolyte, pH and scan rate in the current response of these both drugs was examined to select optimum experimental conditions. By this way, the determination of RMP and its association with HCTZ using SWV and a BDDE was successfully applied in real samples (single and combined dosage forms), with results in close agreement at 95% confidence level with those obtained using high‐performance liquid chromatography.

RP-HPLC Method Development and Validation for Simultaneous Estimation of Telmisartan and Ramipril in pure and Pharmaceutical Dosage forms

A new, precise, accurate, rapid and simple reverse-phase high-performance liquid chromatographic (RP-HPLC) method was developed for the simultaneous estimation of Telmisartan (TEL) and Ramipril (RAM) in pharmaceutical formulation and in bulk. The drugs were estimated using Shiseido C18 (250 x 4.6 mm, 5μm) column. The mobile phase is 0.5% orthophosphoricacid (A), combination of acetonitrile: methanol (70: 30, v/v) (B). A: B in the ratio of (50: 50, v/v) at a flow rate of 1 ml/min was used for the separation. Detection was carried out at 210 nm. Linearity was obtained in the concentration range of 40–120 μg/ml for TEL, 5–15μg/ml for RAM with retention times of 3.218 minutes and 4.803 minutes respectively. The correlation coefficient values were found to be greater than 0.99. Precision studies showed % RSD values less than 2% for both the drugs in all the selected concentrations. The percentage recoveries of TEL and RAM are in the range of 99.91–99.97% and 99.76–99.86% respectively. The assay results of TEL and RAM are 99.91% and 99.82% respectively. The limit of detection (LOD) and limit of quantification (LOQ) were 0.01 μg/ml, 0.8 μg/ml for TEL and 0.1μg/ml, 3μg/ml for RAM respectively. The method was validated as per ICH guidelines. The proposed validated method can be successfully used for the quantitative analysis of Telmisartan (TEL) and Ramipril (RAM) in bulk and commercially available dosage form.

Square-wave adsorptive anodic stripping voltammetric determination of ramipril using an electrochemical sensor based on nanostructured carbon black

A novel and alternative electroanalytical method for the determination of ramipril (RAM) using a glassy carbon electrode (GCE) modified with nanostructured carbon black (CB) is reported.

Poly (amidoamine) dendrimer-mediated hybrid formulation for combination therapy of ramipril and hydrochlorothiazide

We present a dendrimer-based hybrid formulation strategy to explore the potential of poly (amidoamine) PAMAM dendrimers to be used as drug carriers for combination therapy of an anti-hypertensive drug ramipril (RAPL) and a diuretic hydrochlorothiazide (HCTZ). The drug-dendrimer complexes were prepared by phase-equilibration method. The results showed that the solubility of RAPL and HCTZ was dependent on dendrimer concentration and pH of dendrimer solution. The solubility profile of both RAPL and HCTZ dendrimer complexes illustrated a non-linear relationship with dendrimer concentration. At 0.8% (w/v) dendrimer concentration, solubility of RAPL was increased 4.91 folds with amine-terminated while for HCTZ, solubility enhancement was highest (3.72 folds) with carboxy-terminated. The complexes were characterized by Fourier transform infrared spectroscopy, nuclear magnetic resonance analysis and high performance liquid chromatography. In-vitro drug dissolution performance of pure drugs, individual drug loaded dendrimer formulations and hybrid formulations was studied in USP dissolution medium (pH7.0) and in simulated gastric fluid (pH1.2). Dendrimer mediated formulations showed faster and complete dissolution compared to pure RAPL or HCTZ. Surprisingly, similar pattern of dissolution profile was established with hybrid formulations as compared to individual drug loaded dendrimers. The dendrimer-based hybrid formulations were found to be stable at dark and refrigerated conditions up to 5weeks. Conclusively, the proposed formulation strategy establishes a novel multitasking platform using dendrimer for simultaneous loading and delivery of multiple drugs for pharmaceutical applications.

Synthesis and Characterization of Ramipril Embedded Nanospheres of Biodegradable Poly-&lt;I&gt;D&lt;/I&gt;,&lt;I&gt;L&lt;/I&gt;-Lactide-co-Glycolide and Their Kinetic Release Study

Synthesis and Characterization of Ramipril Embedded Nanospheres of Biodegradable Poly-&lt;I&gt;D&lt;/I&gt;,&lt;I&gt;L&lt;/I&gt;-Lactide-co-Glycolide and Their Kinetic Release Study

Spectrophotometric Multicomponent Analysis of Irbesartan, Hydrochlorothiazide and Ramipril in Pharmaceutical Formulations by Chemometric Techniques

Multivariate spectrophotometric methods offer an extensive application for quantification of multicomponent mixtures that exhibit severe spectral overlapping. Partial least Squares (PLS) and Principal componenet Regression (PCR) methods were proposed for the spectrophotometric multicomponent analysis of a ternary mixture consisting of Telmisartan(TEL), Hydrochlorothiazide (HCZ) and Ramipril (RAM) without prior separation. In these chemometric techniques, the measurement of the absorbance values were made in the spectral range from 200-350 nm in the intervals of  = 1 nm at 151 wavelengths in the zero order, first and second derivative spectra of the ternary mixtures of these active ingredients in 0.1 M NaOH. The prepared calibrations of both techniques using absorbance data and concentration matrix data sets were used to predict the concentration of the active ingredients in their ternary, binary and single component mixtures. The optimized models were tested on an external validation set containing synthetic mixtures of the mentioned components. The models were finally used to assay the studied drugs in the commercial formulations. The methods are selective for the determination of telmisartan, hydrochlorothiazide and ramipril and overcome the spectral interference. The prediction values for TEL, HCZ and RAM in both models were found satisfactory.

Ramipril could attenuate thioacetamide‐induced liver fibrosis in rats

Liver fibrosis results from chronic damage to the liver in conjunction with the accumulation of extracellular matrix proteins including collagen which is a characteristic of most types of chronic liver diseases. Thus, the present study aimed to investigate the possible prophylactic and therapeutic effects of an angiotensin converting enzyme inhibitor, ramipril, on liver fibrosis induced by thioacetamide (TAA) in rats. Rats (n=40) were classified into 4 groups (n=10), normal control, fibrotic control and two fibrotic‐treated in which ramipril 2.5 or 5mg/kg, p.o. was given daily for 6 weeks. Liver fibrosis was induced by TAA (200 mg/kg, ip) twice per week for 6 weeks in all groups except in the normal control group. At the end of the 6th week blood samples were withdrawn from orbital sinus for measurement of plasma AST &amp; ALT and animals were sacrificed and then livers were separated &amp; homogenized for measurement of oxidative stress biomarkers (MDA and reduced GSH), inflammatory markers (TNFα, IL10 and MPO) and a fibrotic marker (hydroxyproline). Furthermore, MMP‐13, TIMP‐1, α‐smooth muscle actin and collagen‐1 gene expressions were estimated using RT‐PCR and TGFβ was estimated using western‐plot method. In the fibrotic group plasma aminotransferase activity, MPO activity MDA, TNFα, Hydroxyproline, Collagen‐1, α smooth muscle actin, TIMP‐1 and TGFβ contents increased coupled by decrease in reduced GSH and MMP‐13 contents. Treatment with ramipril reversed most of the measured parameters. The protective effect of the tested agent could be attributed to its anti‐inflammatory, anti‐fibrotic &amp; anti‐oxidant effects.

Method Development, Validation and Pharmacokinetics for Ramipril and Hydrochlorothiazide in Human Plasma and Application in a Bioequivalence Study Based on Healthy Jordanian Volunteers

A simple liquid chromatography mass spectrometric method was developed for quantitative determination of Ramipril (RAM) and Hydrochlorothiazide (HCTZ) simultaneously in human plasma. RAM, HCTZ and the internal standards (RAM-D5, HCTZ-13C, D2) were extracted from human plasma by direct protein precipitation. The chromatographic separation was achieved using ACE 5 C8, (50 mm x 4.6 mm, 5µm) column with gradient elution mobile phase of 0.25 mM Ammonium chloride and methanol. The method validation intends to investigate sensitivity, linearity, precision and accuracy, recovery, matrix effect, specificity and stability according to the European Medicines Agency (EMA) guideline. Standard calibration levels were prepared in pooled human plasma to attain final dynamic range of 0.2 - 20.0 ng/mL for RAM and 1.0 - 150 ng/mL for HCTZ. Clinical bioequivalence study was successfully investigated by application of this validated bioanalytical method in order to evaluate bioequivalence of two commercial products for 5mg RAM/ 25mg Hydrochlorothiazide single dose.

Abstract 024: The Direct Renin Inhibitor Aliskiren Improves Vasodilation and Endothelial Function in Resistance Arteries from Diabetic and Hypertensive Patients

We previously demonstrated that the direct renin inhibitor aliskiren (ALK) significantly reduced the remodeling of subcutaneous resistance arteries of hypertensive patients as compared to the angiotensin-converting enzyme inhibitor ramipril (RAM). Here we questioned whether endothelial function of resistance arteries would improve after 1 year of blood pressure (BP) control with ALK or RAM. Sixteen diabetic patients with mild essential hypertension were randomized to ALK (150-300 mg once daily, n=9) or RAM (5-10 mg once daily, n=7). Subcutaneous resistance arteries were dissected from gluteal biopsy and mounted on a pressurized micromyograph. Endothelium-dependent and -independent relaxations were assessed by concentration-response curves to acetylcholine (1 nM to 100 μM) and sodium nitroprusside (10 nM to 1 mM) respectively, in arteries pre-contracted with norepinephrine (10 μM). Carotid-femoral pulse wave velocity (PWV) was assessed by applantion tonometry. Forearm flow mediated dilation (FMD) was assessed by ultrasounds. The expression of P-eNOS/e-NOS and the markers of oxidative stress nitrotyrosine and LOX-1 were assessed by immunohistochemistry in resistance arteries. Patients were similar for age, sex, BMI and glycemic and metabolic control. Systolic BP was significantly and equally reduced by both ALK and RAM (153±8.9 mmHg reduced to 128±7.3 mmHg and 151±10.6 mmHg reduced to 121±12.1, respectively, P&lt;0.01) whereas diastolic BP was significantly reduced only in ALK-treated but not in RAM-treated patients (94.2±7.17 mmHg reduced to 81.4±6.31 mmHg, P&lt;0.01; and 84.7±12.22 reduced to 78.6±7.48, NS, respectively). PWV and FMD were similar in both groups before and after treatment. Endothelium-dependent vasodilation was improved only by ALK (max dilation 92.5±3.8% vs 50.5±14%, P&lt;0.05) but not by RAM (max dilation 72.9±5.6% vs 61.8±14.5%, NS). Endothelium-independent vasodilation was similar in all the groups. Only ALK increased P-eNOS/eNOS expression (+44% vs before treatment, p&lt;0.05). The markers of oxidative stress were similar in both groups before and after treatment. In conclusion ALK improved endothelial function and induced vasodilation in resistance arteries from diabetic and hypertensive patients.

Simultaneous Quantification of Metolazoneand Ramiprilin Their Combined Dosage Form by First Order Derivative Spectroscopic Method

A simple, accurate and precise first order derivative spectrophotometric method was developed for simultaneous determination of Metolazone (MET) and Ramipril (RAM) in their combined pharmaceutical dosage form. MET and RAM were quantified using first derivative responses at 285nm and 212nm respectively. Methanol was taken as a common solvent. The calibration curve were linear in the concentration range of 5-25 μg/mL for MET and 8-24 μg/mL for RAM. The method was validated and found to be accurate and precise. Developed method was successfully applied for the estimation of MET and RAM in their combined dosage form

Near-Fatal Angioedema Compromising the Airway in a Patient Following Angiotensin Converting Enzyme Inhibitor Formulary Substitution

We present an unusual case of life-threatening angioedema (AE) with airway compromise that occurred after a formulary substitution of one angiotensin converting enzyme inhibitor (ACEI) for another. AE is a known side effect of ACEI therapy. We report a rare case in which a patient who had tolerated years of therapy with enalapril, developed life-threatening AE shortly after being switched to another ACEI: ramipril. AE is of particular importance in airway management as it may present at any point in the emergency ward or hospital stay and it may rapidly become life-threatening if it involves airway compromise. Patient was an 81-year-old female with a past history including peripheral vascular disease, hypertension, and congestive heart failure. Patient was in the status of post femoral artery endarterectomy which subsequently became infected and required an incision and drainage, and subsequent flap closure. The patient was extubated post-operatively. The two main etiologies of AE are mast cell-mediated or kinin-related, although there are less frequent types as well. About 0.1-2.2% of patients treated with ACEI develop recurrent AE, often facial or lip swelling or edema of the tongue and/or larynx. The degree of swelling can be severe: cases of death by asphyxiation following closure of the upper airways have been reported. The interval between starting the ACEI and the appearance of the first AE can be months or even several years, so that making the linkage between the AE and the triggering ACEIs is sometimes unrecognized or recognized late. Because of the very common use of ACEIs, cases of AE are not rare. AE is a medical emergency and requires close monitoring as is routinely provided in an intensive care unit. It is important for practitioners to recognize that AE patients likely have altered airway anatomy and will be difficult intubations. It is crucial to then choose to not sedate or induce unconsciousness prior to securing the airway in these patients. Anticipating difficulty in one’s ability to readily secure an airway requires the presence of experienced airway professionals and the ready availability of specialized equipment. J Med Cases. 2015;6(1):24-26 doi: https://doi.org/10.14740/jmc2019w

Simultaneous Determination and Pharmacokinetic Study of Losartan, Losartan Carboxylic Acid, Ramipril, Ramiprilat, and Hydrochlorothiazide in Rat Plasma by a Liquid Chromatography/Tandem Mass Spectrometry Method.

The monitoring of the plasmatic concentrations of cardiovascular drugs is crucial for understanding their pharmacokinetics and pharmacodynamics. A simple, sensitive, specific, and high-throughput liquid chromatography/tandem mass spectrometry (LC–MS/MS) method was developed and validated for the simultaneous estimation and pharmacokinetic study of losartan (LOS), losartan carboxylic acid (LCA), ramipril (RAM), ramiprilate (RPT), and hydrochlorothiazide (HCZ) in rat plasma using irbesartan (IBS) and metolazone (MET) as internal standards (ISs). After solid phase extraction (SPE), analytes and ISs were separated on an Agilent Poroshell 120, EC-C18 (50 mm × 4.6 mm, i.d., 2.7 μm) column with a mobile phase consisting of methanol/water (85:15, v/v) containing 5 mmol/L ammonium formate and 0.1% formic acid at a flow rate of 0.4 mL/min. The precursor → product ion transitions for the analytes and ISs were monitored on a triple quadrupole mass spectrometer, operating in the multiple reaction monitoring (MRM) mode and switching the electrospray ionization (ESI) mode during chromatography from positive (to detect LOS, LCA, RAM, RPT, and IBS) to negative (to detect HCZ and MET). The method was validated as per the FDA guidelines and it exhibited sufficient specificity, accuracy, and precision. The method was found to be linear in the range of 3–3000 ng/mL for LOS and LCA, 0.1–200 ng/mL for RAM and RPT, and 1–1500 ng/mL for HCZ. The described method was successfully applied to the preclinical pharmacokinetic study of analytes after oral administration of a mixture of LOS (10 mg/kg), RAM (1 mg/kg), and HCZ (2.5 mg/kg) in rats.

Method development of ramipril and atorvastatin calcium capsule by using simultaneous equation method and absorbance ratio method

Ramipril is an angiotensin‐converting enzyme inhibitor and atorvastatin calcium is inhibitor of 3‐hydroxy‐3‐ methylglutaryl‐CoA reductase used in the treatment of hypertension. Simple, precise, rapid and selective simultaneous equation and Q‐analysis methods have been developed for the simultaneous determination of ramipril and atorvastatin fromcombined capsule dosageforms.The methods involve solving of simultaneous equations and Q‐value analysis based on measurementabsorptivity at 210.030 and 246.828 nm, respectively. Linearity lies between 2 and 25 mcg/ml for both drugs. Key words: Absorbance ratio method, atorvastatin, ramipril, simultaneous equation

Development and validation of bioanalytical method for simultaneous estimation of ramipril and hydrochlorothiazide in human plasma using liquid chromatography-tandem mass spectrometry.

The present study describes a novel liquid chromatographic-tandem mass spectrometric (LC-MS/MS) method for the simultaneous estimation of ramipril (RAM) and hydrochlorothiazide (HCTZ) in human plasma using liquid-liquid extraction technique. This method made use of electrospray ionization in positive mode for RAM and in negative mode for HCTZ using triple quadrupole mass spectrometry where carbamazepine was used as an internal standard (IS). Analytes were recovered by methyl tertiary butyl ether:dichloromethane (85:15) subsequently separated on an Enable C18 G column (150 mm × 4.6 mm, 5 μm) using methanol:0.1% formic acid in water (85:15) as a mobile phase, at a flow rate of 0.5 mL/min. Quantification of RAM, HCTZ and IS was performed using multi-reaction monitoring mode (MRM) where transition of m/z 417.2→234.1 (RAM) and 237.0→194.0 (IS) in positive mode and 296.1→205.0 for HCTZ in negative mode. The calibration curve was linear (r(2)>0.99) over the concentration range of 2-170 ng/mL for RAM and 8-680 ng/mL for HCTZ. The intra-day and inter-day precisions were <15% and the accuracy was all within ±15% (at LLOQ level ±20%). Additionally, the LC-MS/MS method was fully validated for all the other parameters such as selectivity, matrix effect, recovery and stability as well. In conclusion, the findings of the present study revealed the selectivity and sensitivity of this method for the simultaneous estimation of RAM and HCTZ in human plasma.