Captopril

Chromatographic Techniques

Chromatographic methods are widely used for the separation and quantification of captopril and its related substances.

Spectrophotometric Methods (e.g., UV-Vis Spectrophotometry)

Spectrophotometric methods, particularly UV-Vis spectrophotometry, offer relatively simple and cost-effective approaches for this compound analysis, especially in pharmaceutical formulations. ijpsm.comajptr.comlew.ro However, this compound itself does not have a strong chromophore in the easily accessible UV-Vis region, with its UV spectrum showing a band around 200 nm. walshmedicalmedia.commedicopublication.com This often necessitates the use of indirect methods or derivatization to form a colored or UV-absorbing species. ijpsm.comlew.ro

Methods based on UV-Vis spectrophotometry often involve reactions that oxidize the thiol group of this compound or form complexes that exhibit measurable absorbance in the visible range. ijpsm.comlew.ro For example, one approach involves the oxidation of this compound by potassium iodate in sulfuric acid medium, followed by the reaction of liberated iodine with starch to form a blue complex with maximum absorbance at 606 nm. ijpsm.com This method obeyed Beer's law in the concentration range of 2-28 ppm. ijpsm.com

Another spectrophotometric method utilizes the reaction of this compound with a bromate-bromide solution in acid medium, followed by the determination of the unreacted bromine using Fluorescein natrium dye, measuring the absorbance at 436 nm. lew.ro This method showed linearity in the range of 0.2-4.50 µg/mL. lew.ro

Note: The specific reaction and resulting chromophore determine the optimal detection wavelength.

Capillary Electrophoresis

Capillary electrophoresis (CE), including capillary zone electrophoresis (CZE), has emerged as an alternative technique for the analysis of this compound and its degradation products. ingentaconnect.comresearchgate.netnih.gov CE offers advantages such as short analysis times, high separation efficiency, and low solvent consumption. ingentaconnect.com

CZE methods for this compound often employ UV detection. ingentaconnect.comresearchgate.net The separation is influenced by factors such as electrolyte concentration, pH, applied voltage, and capillary length. ingentaconnect.com For instance, a CZE method for this compound quantitation used a 20 mM phosphate buffer adjusted to pH 7.0 as the running buffer and an applied voltage of 23.90 kV. ingentaconnect.com The method utilized a fused uncoated silica capillary and UV detection. ingentaconnect.com

The stability of this compound solutions is a consideration in CE analysis, and the use of stabilizing agents like sodium metabisulphite has been investigated to prevent degradation. ingentaconnect.com

CE methods have been developed and validated for the quantitative determination of this compound in pharmaceutical formulations. ingentaconnect.comnih.gov A validated CZE method for this compound in tablets, using cetyltrimethylammonium bromide (CTAB) in a sodium phosphate buffer (pH 5.5; 100 mM) with N-acetyl-L-tyrosine as an internal standard, has been reported. nih.gov This method was found to be stability-indicating and applicable for purity control and the determination of degradation products. nih.gov Another CZE method showed linearity over the range of 5-70 µg/mL with an R² of 0.9995, and limits of quantitation and detection of 5 and 1.5 µg/mL, respectively. ingentaconnect.com

Mass Spectrometry (MS) Techniques for this compound and Metabolites

Mass spectrometry (MS), particularly when coupled with chromatographic techniques like GC or HPLC, provides highly sensitive and selective methods for the analysis of this compound and its metabolites in complex matrices, including biological samples. researchgate.netnih.govredalyc.orgresearchgate.netpensoft.netjapsonline.com

GC-MS methods have been developed for the determination of this compound and its metabolites, such as this compound disulfide dimer and S-methyl this compound. nih.govresearchgate.net These methods often involve derivatization steps to make the analytes amenable to GC separation. researchgate.net For instance, one GC-MS method for this compound and its disulfide metabolites used tributylphosphine to reduce the disulfides to this compound before derivatization with N-ethylmaleimide and subsequent esterification. researchgate.net

LC-MS and LC-tandem mass spectrometry (LC-MS/MS) are powerful techniques for the analysis of this compound in biological fluids like plasma. researchgate.netredalyc.orgpensoft.netjapsonline.com LC-MS/MS methods offer high sensitivity, specificity, and throughput, making them suitable for pharmacokinetic studies and bioequivalence trials. researchgate.netredalyc.orgpensoft.netjapsonline.com These methods typically involve sample preparation steps like protein precipitation or solid-phase extraction (SPE) to isolate the analyte from the biological matrix. researchgate.netjapsonline.com

LC-MS/MS methods often employ reversed-phase columns and gradient elution with mobile phases containing organic solvents (e.g., acetonitrile) and aqueous buffers or acidic modifiers (e.g., formic acid). pensoft.netjapsonline.com Detection is performed using a mass spectrometer in positive or negative ionization mode, often in multiple reaction monitoring (MRM) mode for enhanced selectivity and sensitivity. researchgate.netjapsonline.com

Reported LC-MS/MS methods for this compound in human plasma have demonstrated high sensitivity with low limits of quantification. researchgate.netjapsonline.com For example, one method had a lower limit of quantification of 10 ng/mL, with a linear dynamic range of 10-2000 ng/mL. japsonline.com Another GC-MS method for this compound in human plasma reported a limit of quantification of 0.5 ng/mL. researchgate.net LC-MS/MS is also valuable for investigating the metabolism of this compound and simultaneously measuring multiple compounds, including metabolites. pensoft.net

Derivatization Strategies for this compound Analysis

Derivatization plays a crucial role in the analysis of this compound, particularly for techniques like GC and some spectrophotometric and HPLC methods. tandfonline.comwalshmedicalmedia.comresearchgate.netnih.gov The primary reasons for derivatization are to improve the chromatographic properties (e.g., volatility for GC), enhance detection sensitivity (e.g., by introducing a chromophore or fluorophore), and stabilize the reactive thiol group. walshmedicalmedia.commdpi.com

For GC analysis, derivatization is necessary to convert the polar and relatively non-volatile this compound into a more volatile form. tandfonline.comnih.gov Esterification is one approach used for this purpose. nih.gov Another strategy involves the reaction of the thiol group with reagents like pentafluorobenzyl bromide. tandfonline.comtandfonline.com

In HPLC and spectrophotometric methods, derivatization can be used to create a species that is more easily detectable by UV-Vis or fluorescence detectors. walshmedicalmedia.commdpi.com For instance, complexation with metal ions like Pd(II) has been used as a pre-column derivatization strategy for HPLC with photometric detection. researchgate.net Reactions that produce colored compounds are employed in spectrophotometric methods. ijpsm.comlew.ro

Derivatization can be performed offline (pre-column or pre-capillary) or online (post-column or in-column/in-capillary). walshmedicalmedia.commdpi.comencyclopedia.pub Online derivatization approaches offer advantages such as reduced sample and reagent consumption and potential for automation. mdpi.comencyclopedia.pub

The selection of a derivatization strategy depends on the analytical technique used, the matrix of the sample, and the specific analytical goal (e.g., quantitative analysis of the parent drug or simultaneous determination of metabolites). walshmedicalmedia.com Given the susceptibility of the thiol group to oxidation, derivatization is often employed to stabilize this compound during sample preparation and analysis. walshmedicalmedia.com

Validation of Analytical Methods in Research

The accurate and reliable quantification of this compound is crucial in various research settings, including pharmaceutical analysis, pharmacokinetic studies, and stability assessments. Validated analytical methods ensure that the data obtained is dependable and suitable for its intended purpose. Validation typically involves assessing parameters such as linearity, accuracy, precision, specificity, detection limit, quantitation limit, and robustness, often following guidelines from regulatory bodies like the International Conference on Harmonisation (ICH).

Numerous analytical techniques have been developed and validated for this compound analysis, including High-Performance Liquid Chromatography (HPLC), Gas Chromatography (GC), spectrophotometry, spectrofluorimetry, capillary electrophoresis, and electroanalytical methods acs.org. Reversed-phase HPLC (RP-HPLC) is a frequently employed method in pharmaceutical research due to its versatility and ability to separate this compound from related substances and degradation products scielo.brijpsonline.com. Spectrophotometric methods, often involving derivatization due to this compound's limited UV absorption at higher wavelengths, are also utilized ijpsm.comresearchgate.netajpaonline.com.

Validation studies for this compound analytical methods often focus on different matrices, such as pharmaceutical formulations (tablets) and biological samples (e.g., plasma, tissue homogenates).

Key Validation Parameters and Research Findings

Linearity: This parameter assesses the method's ability to yield results directly proportional to the analyte concentration within a defined range. Research has shown excellent linearity for various methods. For instance, a UV-Vis spectrophotometric method for this compound in tablets demonstrated linearity in the concentration range of 20-60 µg/mL with correlation coefficients of 0.9998 and 0.9994 for absorbance and area under the curve methods, respectively. ijpsm.com. Another spectrophotometric method showed linearity between 2-28 ppm ijpsm.com. An RP-HPLC method for this compound in rabbit plasma exhibited excellent linearity (R² = 0.999) over a range of 3.125–100 µg/mL akjournals.com. For this compound in mucoadhesive tablets, RP-HPLC methods showed linearity with R² values of 0.9993 for assay (5–75 ppm) and 0.9992 for dissolution (5.6–41.7 ppm) japsonline.com.

Accuracy: Accuracy measures the closeness of test results obtained by the method to the true value. It is often expressed as percentage recovery. Validation studies for this compound analysis have reported high recovery rates. A UV-Vis spectrophotometric method showed average percentage recoveries between 95.33% and 101.55% for this compound in patent and generic tablets ijpsm.com. An RP-HPLC method for this compound in rabbit plasma showed mean percentage recoveries ranging from 97% to 100.6% akjournals.com. For this compound in mucoadhesive tablets, RP-HPLC methods demonstrated average recoveries of 100% for the assay method and 99% for the dissolution method japsonline.com. Recovery studies from spiked biological samples like liver, lung, and kidney tissue homogenates and plasma using an HPLC method with derivatization showed relative recoveries in the range of 93.3% to 105.3% psu.edu.

Precision: Precision refers to the agreement among individual test results when the method is applied repeatedly to multiple samplings of a homogeneous sample. It is usually expressed as relative standard deviation (RSD). Low RSD values indicate good precision. Studies have reported good precision for this compound analysis methods. An RP-HPLC method for this compound in rabbit plasma showed intra- and inter-day precision (% RSD) less than 2% akjournals.com. For this compound in mucoadhesive tablets, the RSD values for precision were 1.5% for the assay method and 1.7% for the dissolution method japsonline.com. Repeatability and intermediate precision for an HPLC method for this compound extemporaneous preparations showed %RSD less than 2% researchgate.net.

Specificity: Specificity is the ability of the method to measure the analyte accurately in the presence of other components that may be expected to be present, such as impurities, degradation products, and excipients. Various methods have demonstrated specificity for this compound. RP-HPLC methods are often developed to be stability-indicating, separating this compound from its degradation products, particularly the disulfide dimer scielo.brijpsonline.com. Validation of an RP-HPLC method for related substances in a this compound certified reference material candidate showed sufficient resolution between this compound and this compound disulfide peaks scielo.br. Spectrophotometric methods involving derivatization are designed to react specifically with the thiol group of this compound ijpsm.comresearchgate.net.

Detection Limit (LOD) and Quantitation Limit (LOQ): LOD is the lowest analyte concentration that can be reliably detected, while LOQ is the lowest concentration that can be quantitatively determined with acceptable accuracy and precision. These limits are important for methods used in trace analysis or for detecting impurities. Reported LOD and LOQ values vary depending on the method and matrix. A spectrophotometric method reported LOD and LOQ of 0.08 and 0.26 mg/mL, respectively ijpsm.com. An RP-HPLC method for this compound in rabbit plasma had LOD and LOQ of 3.10 and 9.13 ng/mL, respectively akjournals.com. For an automated zone fluidics-based sensor for dissolution studies, LOD and LOQ were 0.6 µg/mL and 2.78 µg/mL (corresponding to 1% and 5% of maximum expected concentration), respectively mdpi.com. An HPLC method with derivatization reported a detection limit of 200 fmol/20 µL injection volume and an LLOQ of 10 nM in biological samples psu.edu.

Robustness: Robustness evaluates the capacity of the method to remain unaffected by small, deliberate variations in method parameters. Studies assess the impact of minor changes in factors like mobile phase composition, flow rate, pH, and temperature on method performance. An RP-HPLC method validation included robustness testing by evaluating the impact of small variations in wavelength, flow rate, and phosphoric acid concentration, with resulting RSD values less than 2% indicating robustness scielo.brdergipark.org.tr. An automated zone fluidics-based sensor showed satisfactory robustness with variations in flow rate, reagent concentrations, injection volume, and wavelength causing relative errors less than ±5% mdpi.com.

Data Tables

Here are some examples of data extracted from research findings on the validation of analytical methods for this compound:

Table 1: Linearity and Correlation Coefficient of Selected Methods

Table 2: Accuracy (Percentage Recovery) of Selected Methods

Table 3: Precision (% RSD) of Selected Methods

Table 4: Detection Limit (LOD) and Quantitation Limit (LOQ) of Selected Methods

These validation studies highlight the suitability of various analytical methods for the reliable determination of this compound in different research matrices, providing confidence in the quantitative data generated.

Challenges in Captopril Formulation (e.g., Water Solubility, Stability)

This compound's inherent properties pose considerable hurdles in developing stable and controlled-release formulations. A primary challenge is its high water solubility. itmedicalteam.plresearchgate.net While high solubility can be advantageous for immediate release, it makes it difficult to control the dissolution rate for sustained delivery, often leading to dose dumping or a burst effect in sustained-release formulations. itmedicalteam.pl

Another critical challenge is the chemical instability of this compound, particularly its susceptibility to degradation. This compound is unstable in alkaline intestinal pH and undergoes a pseudo-first-order degradation reaction as the pH increases. itmedicalteam.plresearchgate.net The primary degradation pathway involves oxidation, leading to the formation of this compound disulfide (dimer). itmedicalteam.plscielo.brchuv.chscielo.brresearchgate.net This oxidative degradation is a significant concern, especially in aqueous solutions, compromising the drug's therapeutic effect. itmedicalteam.plscielo.br Furthermore, the presence of food has been shown to decrease the bioavailability of oral this compound. itmedicalteam.plmims.comijpsjournal.com The drug also exhibits a mixed absorption profile in the gastrointestinal tract, involving both passive and peptide-carrier mediated transport. itmedicalteam.pl

Approaches for Oral Sustained/Controlled Release Formulations

While the focus is often on sustained release, sublingual formulations have been developed for this compound to achieve a rapid onset of action, particularly in situations requiring a swift reduction in blood pressure, such as hypertensive emergencies. itmedicalteam.plekb.egtishreen.edu.synih.gov Sublingual administration allows for direct absorption into the systemic circulation, bypassing the gastrointestinal tract and first-pass metabolism, leading to a more rapid attainment of peak plasma concentrations compared to oral administration. itmedicalteam.plijpsjournal.comekb.eg Studies suggest that sublingual absorption can be significantly higher than the oral route for some drugs. ekb.eg

Research in this area has focused on formulating sublingual tablets with rapid disintegration properties. The use of superdisintegrants like crosscarmellose sodium, crosspovidone, and sodium starch glycolate is crucial for achieving fast disintegration times, typically under 30 seconds. ekb.egtishreen.edu.sy For instance, one study reported an optimized sublingual formulation with a disintegration time of 13.04 seconds and over 85% drug release within 5 minutes. ekb.egbrieflands.com The addition of agents like citric acid has also been explored to lower the pH in the buccal cavity, potentially enhancing this compound absorption. ekb.eg

Microparticulate systems have been investigated as a means to achieve sustained release and potentially targeted delivery of this compound. itmedicalteam.pl

Studies have explored the use of Bovine Serum Albumin (BSA) as a carrier for this compound microparticles. Microparticles prepared using an emulsification-heat stabilization technique demonstrated controlled release of this compound for up to 24 hours in in vitro studies. itmedicalteam.plnih.govresearchgate.net In vivo studies in hypertensive rats showed that these BSA microparticles resulted in preferential drug targeting to organs such as the liver, lungs, kidneys, and spleen. itmedicalteam.plnih.govresearchgate.net

Cellulose Propionate (CP) has also been utilized in the preparation of this compound microparticles via the solvent evaporation technique. These microparticles exhibited sustained release characteristics, with the release kinetics primarily following a diffusion mechanism. itmedicalteam.plresearchgate.netnih.gov Oral administration of selected CP microparticle formulations to hypertensive rats led to a gradual decrease in systolic blood pressure over a 24-hour period, demonstrating their potential as a sustained-release delivery system. itmedicalteam.plresearchgate.netnih.gov Factors such as polymer molecular weight, composition, and drug-to-polymer ratios influence the encapsulation efficiency and release profiles of these microparticles. researchgate.netnih.gov An initial burst release is sometimes observed, which has been attributed to the dissolution of this compound crystals present on the surface or embedded in the superficial layer of the microparticle matrix. researchgate.netnih.gov

Enhancing Bioavailability Research

This compound's oral bioavailability is approximately 60-75%, and this is reduced when the drug is taken with food. mims.comijpsjournal.com Research into this compound formulations often aims to enhance bioavailability by addressing issues such as degradation, poor absorption in certain parts of the GI tract, and food interactions. itmedicalteam.plresearchgate.net

Beyond sustained-release approaches, other strategies have been explored to improve this compound's bioavailability. Sublingual administration, as mentioned earlier, enhances bioavailability by bypassing the first-pass metabolism. ijpsjournal.comekb.eg Oral dispersible films (ODFs) loaded with this compound have shown promise in enhancing bioavailability. One study reported a significant increase in bioavailability, with the area under the curve (AUC) being 1.43 times higher for the optimized ODF compared to conventional tablets. nih.gov These ODFs also prolonged the time to reach peak plasma concentration (Tmax). nih.gov Semisolid oily matrix systems incorporating ascorbic acid have also been investigated with the goal of improving this compound bioavailability under non-fasting conditions. itmedicalteam.pl The development of microparticulate systems using carriers like BSA is also partly aimed at enhancing bioavailability by localizing the drug at the absorption site. itmedicalteam.pl

Drug Stability Studies

The stability of this compound is a critical factor in its formulation and shelf life. This compound is known to be susceptible to degradation, primarily through oxidation to its disulfide dimer, particularly in the presence of moisture and at higher pH values. itmedicalteam.plscielo.brchuv.chscielo.brresearchgate.net This degradation follows pseudo-first-order kinetics, with pH being a significant influencing factor; the drug is less stable at alkaline pH. itmedicalteam.plresearchgate.netscielo.br

Extensive stability studies have been conducted on this compound in various formulations and storage conditions. Research has evaluated the stability of this compound in different aqueous vehicles, including distilled water, tap water, mineral water, and syrups. scielo.brchuv.chresearchgate.netresearchgate.netnih.govnih.govscielo.br The impact of various additives, such as chelating agents (e.g., EDTA) and antioxidants (e.g., ascorbic acid, sodium metabisulphite), on stability has also been studied. scielo.brchuv.chresearchgate.netresearchgate.netnih.gov

Findings from these studies highlight the importance of formulation composition and storage conditions for maintaining this compound stability. For liquid formulations, the use of EDTA and buffering agents to maintain a low pH (around 3.85) has been shown to improve stability. scielo.brchuv.chnih.gov Storage temperature is a crucial factor, with lower temperatures (e.g., 4°C or 2-8°C) significantly enhancing stability compared to room temperature or higher temperatures. scielo.brchuv.chresearchgate.netnih.govresearchgate.netresearchgate.netnih.govnih.gov Studies have indicated that this compound is more stable in distilled or purified water compared to tap water or mineral water. researchgate.netnih.gov

Coating techniques have also been explored to improve the stability of solid this compound formulations. Coating granules with polymers such as ethylcellulose has been shown to increase this compound stability. researchgate.net Stability studies typically involve monitoring the concentration of intact this compound and its degradation product, this compound disulfide, often using high-performance liquid chromatography (HPLC). scielo.brresearchgate.netresearchgate.netnih.govnih.gov While preservative-free oral solutions are sometimes preferred, their shelf life can be limited, especially when stored under refrigeration, unless supported by comprehensive stability data. scielo.br Research has demonstrated that extemporaneously prepared oral liquid formulations containing stabilizers like disodium edetate at a low pH can maintain chemical stability for extended periods, such as 12 months when stored in glass bottles at room temperature. nih.gov

Here is a summary of some research findings on this compound stability:

Investigation of Captopril's "Pleiotropic" Effects beyond RAAS Inhibition

Beyond its canonical inhibition of ACE and subsequent reduction in angiotensin II levels, research is delving into the "pleiotropic" effects of this compound – effects that are independent of the RAAS pathway. Studies suggest that this compound may influence various biological processes, including inflammation and immune responses. For instance, this compound has been shown to modulate chemotaxis, motility, adhesion, differentiation, activation, and cytokine and chemokine production of immune cells. aai.org Investigations in experimental autoimmune myocarditis models have demonstrated that this compound can significantly reduce the incidence and severity of the condition, accompanied by a reduction in heart weight to body weight ratio and heart weight. aai.org This amelioration was linked to interference with cell-mediated immunity, as evidenced by reduced delayed-type hypersensitivity responses. aai.org Further research is needed to fully elucidate the mechanisms behind these non-RAAS-mediated effects and their potential therapeutic implications in various disease states.

Comparative Studies with Newer Angiotensin System Modulators (e.g., ARBs)

Comparative studies between this compound and newer angiotensin system modulators, such as Angiotensin II Receptor Blockers (ARBs), remain an important area of investigation. These studies aim to assess the relative efficacy and outcomes of these different drug classes in various patient populations and conditions. Early trials like the ELITE (Evaluation of Losartan in the Elderly) study compared losartan (an ARB) with this compound in elderly patients with heart failure, initially suggesting a potential reduction in sudden death with losartan, although a larger subsequent trial (ELITE II) did not find a significant mortality benefit for losartan over this compound. nih.govccjm.orgoup.comnih.gov The VALIANT (Valsartan in Acute Myocardial Infarction) trial also compared valsartan, this compound, and their combination in patients after myocardial infarction complicated by left ventricular dysfunction, heart failure, or both. nih.govajmc.com While ARBs are often considered in patients intolerant to ACE inhibitors due to side effects like cough, ongoing research continues to refine our understanding of the optimal use of these drug classes, either alone or in combination. ccjm.org

Genetic and Genomic Influences on this compound Response (e.g., ACE Genotype)

The influence of genetic and genomic factors on individual responses to this compound is an active area of research. Polymorphisms in the ACE gene, particularly the insertion/deletion (I/D) polymorphism, have been investigated for their potential association with variations in ACE activity and, consequently, the effectiveness of ACE inhibitors like this compound. tandfonline.comnih.govtandfonline.comoup.com While some studies have explored the correlation between ACE I/D genotypes and blood pressure reduction with this compound therapy, findings have been conflicting. tandfonline.comtandfonline.compharmgkb.orgresearchgate.netnih.gov For example, a study in Indonesian hypertensive patients found no statistically significant association between ACE I/D genotypes and blood pressure reduction following this compound treatment. tandfonline.comtandfonline.comnih.gov Conversely, other research has suggested that certain ACE genotypes might be associated with increased or decreased response to this compound in specific patient populations, such as those with diabetes mellitus. pharmgkb.org Further research is needed to identify other genetic and genomic markers that may predict individual responses to this compound and pave the way for personalized medicine approaches. Polymorphisms in the ACE2 gene have also been investigated for their association with hypertension and antihypertensive effects of this compound, particularly in women. researchgate.net

Novel Therapeutic Combinations Involving this compound

Exploring novel therapeutic combinations involving this compound is another avenue of future research. Combining this compound with other classes of drugs may offer synergistic benefits or address limitations of monotherapy. Studies have investigated the combination of this compound with calcium channel blockers, demonstrating an additive effect on blood pressure reduction in patients with essential hypertension, although the effect was noted to be relatively short-acting. ahajournals.orgahajournals.orgnih.gov The combination of this compound with hydrochlorothiazide (HCTZ) has also been explored in sustained-release formulations to potentially improve antihypertensive efficacy. semanticscholar.org Furthermore, research has investigated the combination of this compound with pentoxifylline in reducing proteinuria in diabetic nephropathy, suggesting an additive effect compared to this compound alone. tandfonline.com These studies highlight the potential for developing new combination therapies to optimize patient outcomes.

Elucidation of this compound's Effects in Specific Disease Models (e.g., Infantile Hemangioma, Liver Diseases)

Research continues to explore the effects of this compound in specific disease models beyond its traditional cardiovascular indications. The role of the RAAS in the biology of infantile hemangiomas (IH) has led to investigations into the effect of this compound in this condition. frontiersin.orgamegroups.cnamegroups.orgnih.govjscimedcentral.com Studies have suggested that this compound may induce accelerated involution of IH, supporting the involvement of the RAAS in this proliferative disorder. frontiersin.orgamegroups.cnamegroups.orgjscimedcentral.com However, comparative studies with other treatments, such as propranolol, have shown propranolol to be more effective. amegroups.cnamegroups.org

In the context of liver diseases, studies are investigating the potential protective effects of this compound. Research in animal models of inflammation-induced liver injury has suggested that this compound may improve liver function and attenuate inflammation and oxidative stress. tandfonline.com Additionally, studies have explored the protective effects of this compound against hepatotoxicity induced by certain medications, such as cyclophosphamide, in animal models. ekb.egekb.eg While some research in patients with liver cirrhosis has indicated that this compound inhibits the RAAS, it did not significantly decrease portal venous pressure, suggesting it may not favorably influence the incidence of bleeding in these patients. nih.gov Further research is needed to fully understand the role of this compound in various liver pathologies. Physiologically based pharmacokinetic (PBPK) models are also being developed to predict this compound pharmacokinetics in chronic diseases like chronic kidney disease (CKD) and chronic heart failure (CHF), which could aid in tailoring dosages for these populations. researchgate.netresearchgate.net

Q. What structural and mechanistic principles guided the rational design of captopril as an ACE inhibitor?

this compound was developed using a receptor-based design approach targeting the zinc-binding active site of angiotensin-converting enzyme (ACE). Its sulfhydryl group mimics the carboxyl group of the ACE substrate, enabling competitive inhibition. This design was informed by studies on the venom peptide teprotide, which revealed ACE's catalytic mechanism . Methodologically, crystallographic data and structure-activity relationship (SAR) studies were critical for optimizing binding affinity and selectivity .

Q. How can Quality by Design (QbD) principles be applied to optimize this compound formulations for controlled release?

QbD methodologies involve systematic experimentation with variables like polymer composition (e.g., HPMC K15M and ethylcellulose) to achieve target dissolution profiles. For example, a central composite design (CCD) can model the impact of excipient ratios on drug release kinetics, ensuring robustness in sustained-release formulations. Dissolution testing remains the critical quality attribute (CQA) for validation .

Q. What validated analytical methods are recommended for quantifying this compound in biological matrices?

Reverse-phase high-performance liquid chromatography (RP-HPLC) with UV detection is widely used, offering retention times of ~3.1 minutes under optimized conditions (acetonitrile: 28–36% v/v, pH 2.8–3.6) . For higher sensitivity, LC-HRMS with a mass window of 1 ppm provides selective quantification in dried blood spots, minimizing matrix interference (e.g., m/z 218.0845 for this compound) .

Advanced Research Questions

Q. How do experimental variables (e.g., age, sex, dosage) influence the reproducibility of this compound's therapeutic outcomes in preclinical models?

Studies in renal injury models highlight confounding factors like mixed-sex cohorts and age ranges (3–12 months in rats), which increase data variability. To mitigate this, stratified randomization and covariance analysis (adjusting for age/sex) are recommended. For example, this compound’s efficacy in reducing HW/BW ratios in cardiomyopathic rats was significant only after controlling for these variables .

Q. What mechanisms explain this compound's antiangiogenic effects, and how can these be reconciled with its primary ACE inhibition role?

this compound inhibits endothelial cell migration and metalloproteinases (72-/92-kDa) via zinc chelation, independent of ACE. This biphasic dose-response (effective at <10 µM and millimolar ranges) suggests dual pathways: ACE-dependent vasodilation and ACE-independent antiangiogenesis. In vitro scratch assays and corneal neovascularization models are key for mechanistic validation .

Q. Why do contradictory results arise in studies investigating this compound's metabolic effects (e.g., insulin sensitivity, lipid profiles)?

In SHRSP-ZF rats, this compound failed to improve glucose, insulin, or triglyceride levels despite its antihypertensive action. This discrepancy may stem from tissue-specific ACE expression or compensatory pathways (e.g., RAAS upregulation). Dual inhibition strategies (e.g., combining this compound with PPAR-γ agonists) and tracer-based metabolic flux analysis are proposed to clarify these interactions .

Q. How can novel delivery systems (e.g., transdermal films, biosensors) enhance this compound's therapeutic applicability?

Niosomal-loaded transdermal films improve bioavailability by encapsulating this compound in non-ionic surfactants, achieving sustained release (>12 hours) with minimal dose requirements. For real-time monitoring, smartphone-integrated biosensors using N-CQDs-MnO₂ nanotubes enable dual-mode detection of this compound in plasma (LOD: 0.1 µM) .

Data Contradiction Analysis

Q. How should researchers interpret conflicting data on this compound's lifespan-extending effects in murine models?

The ITP study reported increased median lifespan in mice, but male results were inconclusive due to experimental artifacts. Replication with higher doses (planned by ITP) and strain-specific genetic profiling (e.g., C57BL/6 vs. BALB/c) are advised. Notably, mice lack hypertension-related mortality, necessitating alternative models (e.g., senescence-accelerated mice) .

Q. What methodological refinements address variability in this compound's pharmacokinetic (PK) studies?

Interspecies differences in absorption (e.g., low Caco-2 permeability vs. in vivo bioavailability) require physiologically based pharmacokinetic (PBPK) modeling. Parameterization with plasma protein binding (103.2% recovery in LC-MS) and enterohepatic recirculation data improves predictive accuracy .

Tables for Key Findings