Green-assisted spectrophotometric techniques utilizing mathematical and ratio spectra manipulations to resolve severely overlapped spectra of a cardiovascular pharmaceutical mixture.

Cardiovascular diseases, in particular hypertension and hypercholesterolemia, are two of the main causes of death worldwide. These conditions are silent killer syndromes that need a variety of pharmacological treatments to be effectively controlled. This study introduces novel, environmentally friendly spectrophotometric techniques for the simultaneous determination of telmisartan (TMS) and rosuvastatin calcium (RVS) in their pharmaceutical dosage forms. For the simultaneous determination of the binary mixture, the suggested methods included the dual wavelength method (DWM) which utilizes mainly the absorbance difference at 233 nm and 253 for TMS determination and, the absorbance difference at 274 nm and 310 for RVS determination as the selected wavelengths for each drug is directly proportional to the drug of interest independent on the other interfering component. The Fourier-self deconvolutions method (FSDM) depends on compressing their bandwidth to resolve the overlap. Ratio difference spectrophotometric method (RDSM) that utilizes TMS 35 µg.mL-1 and RVS 20 µg.mL-1, respectively as divisors to produce the ratio spectra for each drug. Further manipulation of the produced ratio spectra was applied for the determination of the two drugs. Mean centering method (MCM) where a suitable wavelength range was chosen to exclusively use the informative portions and prevent experimental spectrum noises. The investigated methods showed good levels of detection and quantification together with excellent linearity. The suggested methods' greenness was evaluated using two different greenness evaluation tools, which showed that the methods were green in terms of several factors, including the safety of the chemicals, instruments, and waste. The validity of the methodologieswas investigated by resolving prepared laboratory mixtureswith varying TMS and RVS ratios. The standard addition method also assured the newly added methods. Finally, statistical analysis using the reported method did not reveal any appreciable differences in terms of accuracy and precision. The developed methods can be employed in quality control laboratories to ascertain the binary mixture due to their high precision and affordability.

Micellar-enhanced and green-assessed first-derivative synchronous spectrofluorimetric approach for concurrent determination of alfuzosin hydrochloride and solifenacin succinate in different matrices: Docking simulation.

Alfuzosin hydrochloride (AZH) is co-formulated with solifenacin succinate (SOS) in Solitral® capsules for treating prostate hyperplasia in patients with overactive bladder syndrome. Herein and for the first time, an ultrasensitive synchronous spectrofluorimetric approach coupled with first-order derivative signal processing was designed for simultaneous determination of AZH and SOS in their pure forms, newly-released pharmaceutical capsules, and human biological fluids. AZH and SOS showed their conventional emission spectra in bi-distilled water at 382 nm and 294 nm after excitation at 325 nm and 250 nm, respectively. The native fluorescence intensities of AZH and SOS were greatly enhanced through micellar formation using sodium dodecyl sulfate surfactant (2%). The proposed approach included the use of synchronous mode at Δλ of 60 nm where the overlap between the studied analytes' fluorescence spectra wasn't completely resolved. The complete resolution was achieved by derivatization of the synchronized spectra to the first-order yielding two zero-crossing points which allowed the determination of AZH and SOS simultaneously without interference at 408 nm and 321 nm, respectively. Under optimum experimental circumstances, good linearities were accomplished over the concentration ranges of (1-24) ng/mL and (4-250) ng/mL with LOD of 0.26 ng/mL and 1.31 ng/mL for AZH and SOS, respectively. The proposed approach was validated successfully according to guidelines adopted by the ICH and compared statistically with the reported LC method with no discernible differences concerning accuracy or precision at p = 0.05. Successful application of the proposed approach achieved with excellent recovery percentages for analysis of the studied analytes in different matrices (pharmaceutical capsules and biological fluids) confirms its suitability for use in QC laboratories and other bioanalytical applications. The proposed approach's greenness was evaluated using two tools namely; penalty points scoring system and green analytical procedure index (GAPI) divulging excellent greenness of this approach relative to the reported LC method. The proposed approach relied chiefly on water as the cheapest and greenest solvent.

Determination of terazosin in the presence of prazosin: Different state-of-the-art machine learning algorithms with UV spectroscopy.

Counterfeit drugs have adverse effects on public health; chromatographic methods can be used but they are costly. In this study, we developed cost-effective and environmentally friendly methodology for the analysis of terazosin HCl (TZ) in the presence prazosin hydrochloride (PZ) using UV spectroscopy in conjunction with machine learning (ML) models. Variable selection algorithms were applied to select most informative spectral variables. Thirty-five ML models were assessed and their performances were compared. The models covered a wide range of prediction mechanisms, such as tree-based, linear, self-organizing maps, neural network, Gaussian process, boosting, bagging, Bayesian models, kernel methods, and quantile regression. The values of the root mean square error (RMSE), coefficient of determination (R2), and absolute mean error (MAE) were obtained for the evaluation of the developed models. According to the results of these performance indices, linear model showed the highest prediction capacity among all other models. RMSE, R2 and MAE values of (0.159, 0.997 and 0.131) and (0.196, 0.99 and 0.161) were obtained for train and test datasets, respectively. The predictive models in this study can be useful for the researchers who are interested to work on the determination of active ingredients in pharmaceutical dosage forms in the presence of interference using UV spectroscopy; therefore, it was used to determine TZ without interference of PZ.

Data on validation using accuracy profile of HPLC-UV method.

The data presented are related to the article entitled "Six Sigma quality approach for HPLC-UV method optimization" Ibrahim et al., 2019. The raw data of HPLC analysis of ascorbic acid (AS), paracetamol (PA) and guaifenesin (GU) are presented. Calibration standards were prepared at six concentrations levels (25%, 50%, 75%, 100%, 125% and 150%) each day and measured in triplicate. Validation standards were prepared at four concentration levels (25%, 60%, 100% and 150%) each day and measured in quintet. Three different series were used for method validation and prepared at the rate of one series per day.

Determination of Atenolol and Trimetazidine in Pharmaceutical Tablets and Human Urine Using a High Performance Liquid Chromatography-Photo Diode Array Detection Method.

A simple RP-HPLC-PDA method for determination of atenolol (ATN) and trimetazidine (TMZ) in human urine and tablets has been developed. Analytes were separated on a Caltrex BI column (125× 4.0 mm, 5 µm) with 25mM potassium dihydrogen phosphate pH 3.3, methanol, and acetonitrile mobile phases. The PDA detector was operated at 210 nm for TMZ and 225 nm for ATN and the flow rate was 1.0 mL/ min. Linearity was obtained over a concentration range of (1.0-100 µg/mL) for both analytes in standard solutions and the method was successfully applied for determination of target analytes in their pharmaceutical tablets. Excellent linearity was also obtained over concentration ranges of (0.25-25 µg/mL) and (0.5-25 µg/mL) in human urine for TMZ and ATN, respectively. A simple liquid-liquid extraction was applied for urine sample clean-up and a gradient method was used for chromatographic separation. The lower limit of quantitation (LOQ) was 0.99 and 0.60 µg/mL for ATN and TMZ, respectively. The limit of detection (LOD) was 0.30 and 0.18 µg/mL for ATN and TMZ, respectively. Inter- and intraday precision and accuracy for ATN were within ±1.89% in pure form and within ±2.85% in urine samples. Inter- and intraday precision and accuracy for TMZ were within ± 3.99% in pure form and within ± 3.19% in urine samples.

Novel spectrophotometric and factor-based multivariate calibration-prediction techniques for determination of two inhibitors of hepatitis C-virus and hepatocellular carcinoma in pure, human urine, and human plasma.

Novel univariate and multivariate factor-based calibration-prediction techniques were validated for simultaneous ultraviolet spectrophotometric determination of ribavirin (RIV), daclatasvir (DAV), sofosbuvir (SOV), and sorafenib (SON) which are co-administered for treatment of hepatocellular carcinoma (HCC) that results from Hepatitis C-virus (HCV) infection in their commercial products and in biological fluids. Determination of these compounds is essential owing to their pharmacotherapeutic benefits. Due to spectral overlapping of RIV, DAV, SOV, and SON, univariate extended derivative ratio (EDR) method and multivariate partial least-squares (PLS) and principal component regression (PCR) methods were used for constructing the calibration curves. The extended derivative ratio (EDR) absorption maxima at 215 nm and minima at 310.5 nm was used for determination of RIV and DAV, respectively and absorption maxima at 240.3 nm and minima at 284.5 nm for determination of SOV and SON, respectively. The linearity was established over the range of 6-42 µg mL-1, 4-16 µg mL-1, 10-70 µg mL-1, and 3-9 µg mL-1 for RIV, DAV, SOV and SON with correlation coefficient (r2) of 0.9997, 0.9997, 0.9999 and 0.9997, respectively. This method was effectively applied to pure, pharmaceutical preparations and to spiked human urine and plasma. PLS and PCR models were established for the determination of the studied drugs in the range of 6-42, 4-16, 10-70 and 3-9 µg mL-1 for RIV, DAV, SOV, and SON, respectively. Furthermore, updating the PLS model (PLS model update) were allowed for the determination of these drugs in spiked human urine, plasma and drug-dissolution test of their tablets. The obtained results were compared to official and reported method showing that there were no significant differences. The results of applying PLS and PCR models for evaluation of RIV, DAV, SOV, and SON in human urine samples as real samples were also encouraging. It is expected that the suitable features of the proposed method make it helpful for biological and clinical applications.

Investigation of anti-Hepatitis C virus, sofosbuvir and daclatasvir, in pure form, human plasma and human urine using micellar monolithic HPLC-UV method and application to pharmacokinetic study.

Simultaneous determination of sofosbuvir (SOF), and daclatasvir (DAC) in their dosage forms, human urine and human plasma using simple and rapid micellar high performance liquid chromatographic method coupled with UV detection (HPLC-UV) had been developed and validated. These drugs are described as co-administered for treatment of Hepatitis C virus (HCV). HCV is the cause of Hepatitis C and some cancers such as liver cancer (hepatocellular carcinoma) and lymphomas in humans. Separation and quantitation were carried out on anonyx™ C8 monolithic (100 × 4.6 mm (i.d.) analytical column maintained at 25 °C. The mobile phase consisted of 0.1 M sodium dodecyl sulfate (SDS) solution containing 20% (V/V) n-propanolol and 0.3% (V/V) triethylamine and pH was adjusted to 6.5 using 0.02 M phosphoric acid, respectively. The retention times of SOF and DAC were 4.8 min, and 6.5 min, respectively. Measurements were made at flow rate of 0.5 mL/min with injection volume of 20 µL and ultraviolet (UV) detection at 226 nm. Linearity of SOF and DAC was obtained over concentration ranges of 50-400, and 40-400 ng/mL, respectively in pure form, 60-300 and 50-300 ng/mL, respectively for human plasma and over 50-400, and 40-400 ng/mL, respectively for human urine with correlation coefficient >0.999. The proposed method demonstrated excellent intra- and inter-day precision and accuracy. The suggested method was applied for determination of the drugs in pure, dosage form, and in real human plasma, real human urine and drug-dissolution test of their tablets. The obtained results have been statistically compared to reported method to give a conclusion that there is no significant differences.

Utility of Cremophor RH 40 as a micellar improvement for spectrofluorimetric estimation of sorafenib in pure form, commercial preparation, and human plasma.

An easy, quick, simple and accurate spectrofluorimetric method was recognized and validated for evaluation of sorafenib (SOR) in pure form and biologically in plasma. Cremophor RH 40 (Cr RH 40) used for enhancing the fluorescence activity of SOR in phosphate buffer (pH 7). Cr RH 40 improved the native fluorescence of SOR remarkably in water. The fluorescence spectrum of SOR was observed at 405 nm after excitation at 265 nm. The linearity appeared to be in the range of 5 to 600 ng ml-1 for pure and from 9 to 500 ng ml-1 for plasma using the protein precipitation (ppt) method while from 10 to 500 ng ml-1 for plasma using liquid-liquid extraction method. The precisions and the accuracy of the estimated method gave satisfactory results. The recommended method was effectively applied for determination of SOR in human plasma with high recovery values. The results of some compounds that are possibly found in plasma were studied. The proposed method was also focused on real volunteers and a drug dissolution test.

A novel spectrofluorimetric method for determination of imatinib in pure, pharmaceutical preparation, human plasma, and human urine.

The following paper represents a simple, highly sensitive, responsive validated and developed spectrofluorimetric method for estimation of imatinib (IMB) in its pure, commercial preparation, human urine and human blood plasma. The calibration curve was in the range 4-900 ng ml-1 for pure form and urine and 8-900 ng ml-1 for plasma in a medium contains carboxymethyl cellulose (CMC) and acetate buffer (pH 5) with excitation wavelength (λex ) 230 nm and emission wavelength (λem ) 307 nm. The limit of detection (LOD) was 0.37 ng ml-1 for the pure form, 0.64 ng ml-1 for human urine, and 0.70 ng ml-1 for human plasma, while the limit of quantitation (LOQ) was 1.2 for pure form, 1.91 for urine and 2.1 for plasma. The suggested method was successfully applied for evaluation of IMB in tablets within 99% mean percentage recovery. The excipients that are usually used as additives in pharmaceutical dosage form did not interfere with the suggested method. The method was efficiently used for estimation of IMB in human urine and human plasma. The effect of some cations that might be present in urine and plasma was also studied. The method was also focused on human volunteers and in vitro drug release.

Utility of 4-chloro-7-nitrobenzofurazan (NBD-CI) for the Spectrophotometric and spectrofluorometric determination of several antihistamine and antihypertensive drugs.

New, sensitive, and selective spectrophotometric and spectrofluorometric methods have been developed for determination of clemastine hydrogen fumarate (Clem), loratadine (Lor), losartan potassium (Los), and ramipril (Ram) in both pure form and pharmaceutical formulations using 4-chloro-7-nitrobenzofurazan (NBD-CI), which is a highly sensitive chromogenic and fluorogenic reagent. The relation between absorbance at 470, 467, 471, and 469 nm and the concentration was linear over the ranges 5-35, 10-100, 10-90, and 10-120 microg/mL for Clem, Lor, Los, and Ram, respectively. The complexation products were also measured spectrofluorometrically at the emission wavelength 535 nm for Clem, Lor, and Ram and at 538 nm for Los with excitation at 477 and 452 nm for Clem and Lor, respectively, and 460 nm for both Los and Ram. The fluorescence intensity was directly proportional to the drug concentration over the ranges 0.05-0.5, 5-20, 1-6, and 2-15 microg/mL for Clem, Lor, Los, and Ram, respectively. The methods were successfully applied for the determination of the studied drugs in pharmaceutical dosage forms with excellent recovery.

Spectrofluorimetric determination of etodolac, moxepril HCl and fexofenadine HCl using europium sensitized fluorescence in bulk and pharmaceutical preparations.

A simple, selective and sensitive luminescence method has been developed for the assay of etodolac (I), moxepril HCl (II) and fexofenadine HCl (III) in bulk drug and pharmaceutical formulations. The method is based on the luminescence sensitization of europium (Eu(3+)) by complexation with the studied drugs. The fluorescence intensities of the products were measured at 667 nm for (I) and at 615 for (II) and (III) while exciting at 276 for all the studied drugs. The fluorescence intensity was directly proportional to the concentration over the range (20-280), (40-240) and (30-80) ng/ml with limits of detection (LOD) = 0.93, 0.92 and 0.95 µg/ml for drugs I, II and III respectively. Optimum conditions for the formation of the complex in methanol were carefully studied. The proposed method was successfully applied for the assay of the studied drugs in pharmaceutical formulations with excellent recovery.

Monitoring phospholipids for assessment of ion enhancement and ion suppression in ESI and APCI LC/MS/MS for chlorpheniramine in human plasma and the importance of multiple source matrix effect evaluations.

Biological matrix effects are a source of significant errors in both electrospray (ESI) and atmospheric pressure chemical ionization (APCI) LC/MS. Glycerophosphocholines (GPChos) and 2-lyso-glycerophosphocholines (2-lyso GPChos) are known to fragment to form ions at m/z 184 and m/z 104, respectively. Phospholipids were used as markers to evaluate matrix effects resulting in both ion suppression and enhancement using ESI and APCI modes in the determination of chlorpheniramine in human plasma. Results revealed that GPChos and 2-lyso GPChos demonstrated very low ionization efficiency in the APCI mode, post-column infusion experiments were performed to confirm that suppression and enhancement matrix ionization effects coincided with the elution profiles of the phospholipids. The mean matrix effect for chlorpheniramine using APCI was 75% less than the mean matrix effect in ESI, making APCI the ionization method of choice initially even though the absolute response was lower than in the ESI mode. The resulting APCI method showed acceptable results according to the FDA guidelines; however, a multiple source relative matrix effects study demonstrated variability. It was concluded that an absolute matrix effects study in one source of biological fluid may be not sufficient to ensure the validity of the method in various sources of matrix. In order to obviate the multiple matrix source variability, we employed an isotopically labeled internal standard for quantification of chlorpheniramine in the ESI mode. An additional validation was completed with the use of chlorpheniramine-d(6) as the internal standard. This method met all acceptance criteria according to the FDA guidelines, and the relative matrix affects study was successful.

Assessment of matrix effects and determination of niacin in human plasma using liquid-liquid extraction and liquid chromatography-tandem mass spectrometry.

A simple, sensitive and rapid liquid-liquid extraction method for the analysis of nicotinic acid (niacin) and its labeled internal standard nicotinic acid-d4 (niacin-d4) in human plasma was developed and validated. The analyte and its internal standard were isolated from acidified plasma using a single liquid-liquid extraction procedure with methyl-t-butyl ether. The extracted samples were analyzed by liquid chromatography-tandem mass spectrometry in positive electrospray ionization mode with multiple reaction monitoring. The calibration curves were linear in the measured range between 5 and 1000 ng/mL and the limit of detection was calculated as 122 pg/mL. The method required 250 microL of human plasma and the total run time between injections was 3.5 min. Matrix effects were assessed by post-column infusion experiments, phospholipids monitoring and post-extraction addition experiments. The extraction of phospholipids and niacin from plasma was studied under acidic, neutral and basic conditions. Acidic conditions were optimal for both the recovery of niacin and the removal of phospholipids; the degree of matrix effects for niacin was determined to be 2.5%. It was concluded that effective removal of matrix components can overcome low recovery issues associated with liquid-liquid extractions of polar analytes.

Potentiometric membrane sensor for the selective determination of pethidine in pharmaceutical preparations and biological fluids.

The construction and general performance characteristics of a novel potentiometric PVC membrane sensor based on pethidine-phosphomolybdate as electroactive material for the determination of pethidine are described. This sensor exhibits fast, stable and near-Nernstain response 55.24 +/- 0.1, over the concentration range 1.10(-2)-1.10(-5)M for pethidine-phosphomolybdate over pH 2-7. No interferences are caused by many organic, inorganic cations, alkaloids and amino acids. The sensor proved useful for determining pethidine in pure forms, pharmaceutical injections and monitoring the content uniformity assay of ampoules. The designed sensor also show good accuracy for the determination of pethidine in biological fluids.

Monitoring phospholipids for assessment of matrix effects in a liquid chromatography-tandem mass spectrometry method for hydrocodone and pseudoephedrine in human plasma.

Matrix effects resulting in ion suppression or enhancement have been shown to be a source of variability and inaccuracy in bioanalytical mass spectrometry. Glycerophosphocholines may cause significant matrix ionization effects during quantitative LC/MS/MS analysis and are known to fragment to form characteristic ions (m/z 184) in electrospray mass spectrometry. This ion was used to monitor ion suppression effects in the determination of hydrocodone and pseudoephedrine in human plasma as a means to track and avoid these effects. The m/z 184 ion fragment was detected in both plasma extracts and solutions of phosphatidylcholine. Post-column infusion studies showed that the ion suppression for both drugs and internal standards correlated with the elution of phospholipids. HPLC conditions were adjusted to chromatographically resolve the peaks of interest from the phospholipids. Upon repeated injection, the elution time of the phospholipids decreased while elution of the analyte peaks remained unchanged. This resulted in co-elution and significantly affected peak shape and internal standard response for the analytes. It was decided to use the phospholipid fragment to monitor this matrix effect in validation samples. The resulting method demonstrated intra-day and inter-day precision within 4.5 and 5.6% for hydrocodone and pseudoephedrine, respectively, and accuracy within 8.9 and 8.7% for hydrocodone, and pseudoephedrine, respectively. There was no statistically significant difference in the internal standard response for the determination with and without monitoring the phospholipid fragment ion. We found that monitoring the phospholipid fragment was useful in method development to avoid the matrix effects, and in routine analysis to provide a practical way to ensure the avoidance of matrix effects in each individual sample.

New colorimetric methods for the determination of trazodone HCl, famotidine, and diltiazem HCl in their pharmaceutical dosage forms.

Two sensitive and simple spectrophotometric methods are developed for the determination of trazodone HCl, famotidine, and diltiazem HCl in pure and pharmaceutical preparations. The methods are based on the oxidation of the cited drugs with iron(III) in acidic medium. The liberated iron(II) reacts with 1,10-phenanthroline (method A) and the ferroin complex is colorimetrically measured at 510 nm against reagent blank. Method B is based on the reaction of the liberated Fe(II) with 2,2-bipyridyl to form a stable colored complex with lambda(max )at 520 nm. Optimization of the experimental conditions was described. Beer's law was obeyed in the concentration range of 1-5, 2-12, and 12-32 microg mL(-1) for trazodone, famotidine, and diltiazem with method A, and 1-10 and 8-16 microg mL(-1) for trazodone and famotidine with method B. The apparent molar absorptivity for method A is 1.06x10(5), 2.9x10(4), 1.2x10(4) and for method B is 9.4x10(4 )and 1.6x10(4), respectively. The suggested procedures could be used for the determination of trazodone, famotidine, and diltiazem, both in pure and dosage forms without interference from common excipients.

Spectrophotometric methods for determination of enalapril and timolol in bulk and in drug formulations.

Two simple and accurate spectrophotometric methods for determination of timolol and enalapril maleate are described. The first method is based on chelate formation with palladium(II) chloride in buffered medium. The second method is based on the formation of the colored complex between palladium(II), eosin, and the two cited drugs using methylcellulose as surfactant to increase the solubility and intensity of the formed complexes. Under optimum conditions the complexes showed maximum absorption at 369.4 nm and 362.8 nm for timolol and enalapril maleate, respectively, in the first method and 552.2 and 550.6 nm for the second method. Apparent molar absorptivities were 1.8 x 10(3) and 1.3 x 10(3) and Sandell's sensitivities were 5.9 x 10(-4) and 2.7 x 10(-4) for timolol and enalapril maleate in the first method; in the second method molar absorptivities were 2.8 x 10(4) and 1.1 x 10(4) while Sandell's constants were 9.1 x 10(-3) and 2.3 x 10(-3) for timolol and enalapril maleate. The solutions of the complexes obeyed Beer's law in the concentration ranges 20-200 micro g mL(-1) and 50-300 micro g mL(-1) for timolol and enalapril maleate, respectively. In the second method, because the reaction was more sensitive the ranges were reduced to 1.6-16 micro g mL(-1) for timolol 8-56 micro g mL(-1) for enalapril maleate. The proposed methods were applied to the determination of the two drugs in their pharmaceutical formulation.

Potentiometric determination of famotidine in pharmaceutical formulations.

Two new potentiometric methods for determination of famotidine in pure form and in its pharmaceutical tablet form are developed. In the first method, the construction of plasticised poly(vinyl chloride) (PVC) matrix-type famotidine ion-selective membrane electrode and its use in the potentiometric determination of famotidine in pharmaceutical preparations are described. It is based on the use of the ion-associate species, formed by famotidine cation and tetraphenyl borate (TPB) counterion. The electrode exhibited a linear response for 1 x 10(-3)-1 x 10(-5) M of famotidine solutions over the pH range 1-5 with an average recovery of 99.26% and mean standard deviation of 1.12%. Common organic and inorganic cations showed negligible interference. In the second method, the conditions for the oxidimetric titration of famotidine have been studied. The method depends on using lead(IV) acetate for oxidation of the thioether contained in famotidine. The titration takes place in presence of catalytic quantities of potassium bromide (KBr). Direct potentiometric determination of 1.75 x 10(-2) M famotidine solution showed an average recovery of 100.51% with a mean standard deviation of 1.26%. The two methods have been applied successfully to commercial tablet. The results obtained reveal good percentage recoveries, which are in good agreement with those obtained by the official methods.

Spectrophotometric and AAS determination of ramipril and enalapril through ternary complex formation.

Two sensitive, spectrophotometric and atomic absorption spectrometric procedures are developed for the determination of two antihypertensive agents (enalapril maleate and ramipril). The spectrophotometric procedures for the two cited drugs are based on ternary complex formation. The first ternary complex (copper(II), eosin, and enalapril) was estimated by two methods; the first depends on its extraction with chloroform measuring at 533.4 nm. Beer's law was obeyed in concentration range from 56 to 112 microg ml(-1). The second method for the same complex depends on its direct measurement after addition of methylcellulose as surfactant at the pH value 5 at 558.8 nm. The concentration range is from 19 to 32 microg ml(-1). The second ternary complex (iron(III), thiocyanate, and ramipril) was extracted with methylene chloride, measuring at 436.6 nm, with a concentration range 60-132 microg ml(-1). The direct atomic absorption spectrometric method through the quantitative determination of copper or iron content of the complex was also investigated for the purpose of enhancing the sensitivity of the determination. The spectrophotometric and atomic absorption spectrometric procedures hold their accuracy and precision well when applied to the determination of ramipril and enalapril dosage forms.