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Acta Poloniae Pharmaceutica ñ Drug Research, Vol. 67 No. 2 pp. 137ñ143, 2010 ISSN 0001-6837 Polish Pharmaceutical Society

IDENTIFICATION AND DETERMINATION OF ANTIHYPERTONICS FROM THE GROUP OF ñ CONVERTASE INHIBITORS BY DENSITOMETRIC METHOD IN COMPARITION WITH HPLC METHOD

ELØBIETA WYSZOMIRSKA1*, KRYSTYNA CZERWI—SKA1 and ALEKSANDER P. MAZUREK1,2

1Department of Basic and Applied Pharmacy, National Medicines Institute, 30/34 Che≥mska St., 00-725 Warszawa, Poland 2Department of Drug Chemistry, Medical University of Warsaw, 1 Banacha St., 02-097 Warszawa, Poland

Abstract: Conditions have been elaborated for the identification of all the compounds belonging to the group of angiotensin convertase inhibitors: , , , , , , , , , , , and zofenopril by thin-layer chromatography. The selected conditions were used to design the densitometric method for the content determination of the above mentioned compounds in substances and medicines. The statistical data obtained for the designed method indicate ade- quate accuracy and precision.

Keywords: lisinopril, quinapril, ramipril, spirapril, moexipril, trandolapril, benazepril, cilazapril, fosinopril, captopril, enalapril, imidapril, zofenopril, , antihypertonics, densitometric metod

Arterial is one of the most com- the body they are subjected to hydrolysis into acids, mon cardiovascular disorders. Due to large inci- being capable of competitive inhibition of ACE dence of the disorder and the fact that it is an agent activity. that contributes to the development of arteriosclero- ACE inhibitors differ in terms of pharmacoki- sis and its clinical forms ñ coronary disease, cardiac netic properties and affinity for ACE. This is related infarction, cerebral stroke, it is considered to be a to the strength and time of their activity. social disease. At present, ACE inhibitors are the first-choice The principle action of hypotensive medicines medicines used in the treatment of hypertension. is based on controlling blood pressure in various They may also be used in the treatment of ischemia pressure points. ñ angiotensin ñ aldosterone and heart failure. Their active metabolites created as system plays an important role in controlling blood a result of hydrolysis cause the fall in ACE activity, pressure and volume of body fluids. This has been a a decrease in releasing aldosterone, an increase in crucial agent in the necessity of searching for the the concentration of vaso-dialytic kinins and medicines inhibiting the renin ñ angiotensin activity, prostaglandins and indirectly reducing synthesis of including, among others, ACE (angiotensin convert- catecholamines and general sympathetic activity. ing enzyme) inhibitors. These inhibitors are dipep- This results in diastole of vessels and reduction of tides or compounds which are structurally very sim- circulating blood volume, which leads to the drop in ilar. One of the analogies is the presence of S-pro- blood pressure and reduction of peripheral resist- line in a cyclic molecule whose ring may be ance (1-3). replaced with another one, provided that configura- In the recent years, all medicines from the fol- tion S is maintained at C2. The SH group containing lowing group have been subjected to research: moiety, present in some ACE inhibitors, may be lisinopril, quinapril, ramipril, spirapril, moexipril, replaced with another one, e.g. with S-alanine. trandolapril, benazepril, cilazapril, fosinopril, capto- A majority of converting inhibitors are ethyl pril, enalapril, imidapril, zofenopril and perindopril. esters of appropriate acids. Esterases cause that in From the literature on the subject it can be conclud-

* Corresponding author: e mail: [email protected]

137 138 ELØBIETA WYSZOMIRSKA et al. ed that in the recent years the following methods Imidapril HCl, Zofenopril Ca, Perindopril, Lisinopril ñ have been used for determination of these com- ratiopharm tablets 20 mg, Accupro 20 tablets 20 mg, pounds: HPLC with the use of various detectors, Tritace 10 tablets 10 mg, Quadropril tablets 6 mg, spectrofotometric and fluorometric methods, poten- Cardiotensin 7.5 tablets 7.5 mg, Gopten capsules 2 mg, tiometry, densitometry, gas chromatography and Lotensin tablets 10 mg, Inhibace coated tablets 1 mg, capillary electrophoresis. Monopril tablets 20 mg, Captopril tablets 12.5 mg, The HPLC method and spectrofotometric Enalapril tablets 20 mg, Tanatril tablets 20 mg, Zofenil detector as well as C18 column (4-14) was used for 30 coated tablets 30 mg . identification and determination of benazepril, tran- Analytically pure and high-purity reagents for dolapril, cilazapril, fosinopril, enalapril, quinapril HPLC, Merck HPTLC F254 pre-coated plates (glass), and moexipril, whereas C8 column (15-17) was Silica gel 60 layers (20 ◊ 10 cm), Camag used for determination of: ramipril, benazepril and Chromatographic chamber (20 ◊ 10 ◊ 5 cm), Hanau lisinopril. UV Lamp, Camag automatic applicator, Shimadzu CS The HPLC method with the use of mass spec- 9000 densitometer, Shimadzu liquid chromatograph trometry detector (18-27) was also used for identify- with SPD-10 AVVP spectrofotometric detector, SCL- ing and determining zofenopril, fosinopril, enalapril, 10 AVP auto-sampler, and LC-10 AT VP pump. quinapril, ramipril, trandolapril, cilazapril and imi- dapril. QUALITATIVE ANALYSIS Spectrofotometric determination was used for ramipril (28, 29) after transformation in colored Standard solutions were prepared as follows: derivatives, and cilazapril (30) and fosinopril (31) lisinopril, quinapril, ramipril, spirapril, moexipril, determined in two-element medicines with trandolapril, benazepril, cilazapril, fosinopril, capto- hydrochlorothiazide. pril, enalapril, imidapril and perindopril in methanol Fluorometric method was used for determina- as well as zofenopril in acid methanol (2 mL 85% o- tion of ramipril after derivatization (29). phosphoric acid in 100 mL of methanol) of the fol- Captopril was determined with potentiometric lowing concentrations: 2, 0.1, 0.01 and 0.001 method using enantioselective electrodes (32-33). mg/mL. Quantities of 10, 5, 2.5, 1, 0.5, 0.25, 0.1, Gas chromography method was used for determin- 0.05, 0.025, 0.01 and 0.005 µg of active substances ing moexipril with the use of capillary column DB- were put as spots on glass chromatoplates HPTLC

1 (34), whereas benazepril with hydrochlorothiazide GF254 (2 cm from the bottom of the plate and 2 cm was determined by densitometric method (35). from edges) and unrolled up to 1 cm from the top of Capillary electrophoresis method was used for the plate in 6 various mobile phases:1) ethyl acetate determining cilazapril (36) and its active metabolite ñ methylene chloride ñ methanol ñ ammonia 25% ñ cilazaprilat, isolated from urine. Available litera- (30 : 25 :2 : 1, v/v), 2) toluene ñ glacial acetic acid ture does not comprise any publications on deter- (30 : 10, v/v) with saturation, 3) chloroform ñ mining spirapril. methanol ñ glacial acetic acid (30 : 5 : 1, v/v), 4) The HPLC method, widely used for analysis of toluene ñ glacial acetic acid ñ methanol (75 : 25 : 10, compounds from the group of convertase inhibitors, v/v) with saturation, 5) benzene ñ glacial acetic acid requires expensive equipment and high purity (3 : 1, v/v) with saturation, 6) n-butanol ñ glacial reagents, which significantly increase the cost of acetic acid ñ water (3 : 1 : 1, v/v). determination. Therefore, an attempt has been made After drying the plates with air, the position of to develop a sensitive, less expensive and time con- spots was determined under UV light with wave- suming method of identification and determination length of 254 nm, and then the plates were exposed of lisinopril, quinapril, ramipril, spirapril, moexipril, to iodine vapors. In qualitative analyses, Rf values trandolapril, benazepril, cilazapril, fosinopril, capto- were determined and detection limits were estab- pril, enalapril, imidapril, zofenopril and perindopril lished for all compounds investigated in all systems. in medicines. The results have been presented in Tables 1 and 2.

EXPERIMENTAL QUANTITATIVE ANALYSIS Determination of the content by densitometric Materials and apparatus method

Lisinopril 2 H2O, Quinapril HCl, Ramipril, For captopril, enalapril and spirapril ñ mobile Spirapril HCl, Moexipril HCl, Trandolapril, Benazepril, phase 3, for ramipril, quinapril, lisinopril, moexipril, Cilazapril, Fosinopril Na, Captopril, Enalapril Maleate, trandolapril, benazepril, cilazapril, fosinopril and Identification and determination of antihypertonics from the group of angiotensin convertase inhibitors by... 139

Table 1. Rf values for the tested compounds (grey fields refer to the mobile phase selected for the quantitative determination of a given compound). Tested Mobile Mobile Mobile Mobile Mobile compound phase 2 phase 3 phase 4 phase 5 phase 6 Lisinopril 0 0 0 0 0.29 Quinapril 0 0.91 0.05 0 0.85 Ramipril 0.06 0.84 0.06 0.06 0.82 Spirapril 0 0.84 0.05 0 0.84 Moexipril 0.06 0.84 0.12 0.11 0.82 Trandolapril óó 0.76 óó- 0.36 0.87 Benazepril 0.12 0.76 0.18 0.22 0.89 Cilazapril 0.06 0.83 0.09 0.08 0.82 Fosinopril 0.57 0.85 0.59 0.71 0.63 Captopril 0.29 0.74 0.29 0.32 0.71 Enalapril 0.04 0.63 0.02 0.04 0.66 Imidapril 0 0.52 0.15 0 0.58 Zofenopril 0.45 0.95 0.88 0.55 0.85

Mobile phases: 1) ethyl acetate : dichloromethane : methanol : 25% ammonia (30:25:2:1, v/v) ñ Rf = 0 for all tested compounds; 2) toluene : glacial acetic acid (30:10, v/v) with saturation; 3) chloroform : methanol : glacial acetic acid (30:5:1, v/v); 4) toluene : glacial acetic acid : methanol (75:25:10, v/v) with saturation; 5) benzene : glacial acetic acid (3:1, v/v) with saturation; 6) n-butanol : glacial acetic acid (3:1:1, v/v)

Table 2. Detection limits of tested compounds (grey fields refer to the mobile phase selected for the quantitative determination of a given compound). Mobile phase 2 Mobile phase 3 Mobile phase 4 Mobile phase 5 Mobile phase 6 Tested UV I UV UV UV UV compound odine [µg] Iodine [µg] Iodine [µg] Iodine [µg] Iodine [µg] [µg] [µg] [µg] [µg] [µg] Lisinopril 5 0.5 5 0.5 5 0.5 5 0.5 1 1 Quinapril 5 5 5 5 5 - 5 - 1 1 Ramipril 5 5 10 5 5 5 5 5 3 3 Spirapril 5 1 1 1 5 - 5 - 1 1 Moexipril 0.5 0.2 0.5 0.05 0.5 0.5 0.5 0.2 0.5 0.5 Trandolapril - - 1 0.5 - - 5 0.5 2 1 Benazepril 0.2 0.5 0.2 0.1 0.2 0.5 0.2 0.2 0.2 0.2 Cilazapril 0.5 0.02 0.5 0.1 0.5 0.2 0.5 0.2 0.5 0.5 Fosinopril 1 0.5 1 0.5 5 1 0.5 0.2 0.5 0.5 Captopril 5 5 3 1 5 5 5 3 5 0.1 Enalapril 2.5 5 1 1 5 5 3 3 5 0.5 Imidapril 5 0.2 1 0.5 5 0.2 5 0.2 0.5 0.5 Zofenopril 0.025 0.025 0.2 0.2 0.025 0.025 0.025 0.1 0.025 0.05

Mobile phases: 2) toluene ñ glacial acetic acid (30:10, v/v) with saturation; 3) chloroform ñ methanol ñ glacial acetic acid (30:5:1, v/v); 4) toluene ñ glacial acetic acid ñ methanol (75:25:10, v/v) with saturation; 5) benzene ñ glacial acetic acid (3:1, v/v) with saturation; 6) n- butanol ñ glacial acetic acid (3:1:1, v/v) 140 ELØBIETA WYSZOMIRSKA et al. imidapril ñ mobile phase 6 and for zofenopril ñ centrations of: 3 mg/mL for captopril, 2 mg/mL for mobile phase 2 were used as optimal. enalapril, quinapril, lisinopril, ramipril and fosino- Densitometric analysis was conducted using pril, 1.8 mg/mL for spirapril, 1 mg/mL for Shimadzu CS 9000 densitometer. Plates were placed benazepril and cilazapril, 0.75 mg/mL for moexipril in the chamber of the apparatus. Slot dimensions and imidapril, 0.25 mg/mL for zofenopril (in acid were 0.4 ◊ 0.4 mm. The measurements were made methanol) and 0.2 mg/mL for trandolapril. by zigzac method with the width of deflections 14 The isolation of components from the tablets mm. The maximal wavelengths were: for: lisinopril and capsules was carried out by means of methanol, ñ 213 nm, quinapril ñ 215 nm, ramipril ñ 210 nm, except for the Zofenil tablets where the isolation was spirapril ñ 220 nm, moexipril ñ 276 nm, trandolapril conducted by means of acid methanol, by shaking ñ 210 nm, benazepril ñ 247 nm, cilazapril ñ 225 nm, the samples for 15 min in the ultrasound bath and 30 fosinopril ñ 222 nm, captopril ñ 212 nm, enalapril ñ min in a mechanical shaker. The solutions were drib- 210 nm, imidapril ñ 227 nm, zofenopril ñ 238 nm. bled through filters with a pore size of 0.45 µm. Determination of regression curves The concentration ranges of standard methanol Determintion of content solutions and drug solutions for all analyzed com- Ten µL of all the prepared solutions, analyzed pounds were as follows: for lisinopril and medicines and standards, were placed as spots on

Lisinoprilñ ratiopharm, tablets 20 mg, quinapril and glass chromatoplates HPTLC GF254 (2 cm from the Accupro 20 tablets 20 mg and spirapril and bottom of the plate and 2 cm from edges) and devel- Quadropril tablets 6 mg ñ 0.25 ñ 4 mg/mL; for oped up to 1 cm from the top of the plate in mobile ramipril and Tritace 10 tablets 10 mg and tran- phases established as optimal for respective com- dolapril and Gopten capsules 2 mg ñ 0.5 ñ 3 mg/mL; pounds (see above). After drying, densitometric for moexipril and Cardiotensin tablets 7.5 mg ñ 0.1 measurements were conducted at predetermined ñ 1.5 mg/mL; for benazepril and Lotensin tablets 10 wavelengths. The results and statistical assessment mg ñ 0.1 ñ 2 mg/mL; for cilazapril and Inhibace are presented in Tables 3 and 4. coated tablets 1 mg ñ 0.2 ñ 2.0 mg/mL, for fosino- In addition, in order to make a comparison of pril and Monopril tablets 20 mg ñ 0.2 ñ 4 mg/mL; the designed method, the assay of lisinopril, for captopril and Captopril tablets 12.5 mg and quinapril, ramipril, spirapril, moexipril, trandolapril, enalapril and Enalapril tablets 20 mg ñ 1 ñ 5 mg/mL; benazepril, cilazapril, fosinopril, captopril, for imidapril and Tanatril tablets 20 mg ñ 0.25 ñ 2 enalapril, imidapril and zofenopril in the tested sub- mg/mL; for zofenopril and Zofenil coated tablets 30 stances and preparations was performed by HPLC mg in acid ethanol ñ 0.05 ñ 0.5 mg/mL. method that is routinely used for determining the All tests were shaken for 15 min on ultrasound content of the above mentioned compounds in med- bath and 30 min in mechanical shaker. The solutions icines. For determining cilazapril, imidapril, moex- were filtered via filters of the pore size 0.45 µm. ipril, captopril, fosinopril, zofenopril, ramipril, Ten µL of the prepared solutions were spotted benazepril and spirapril C18 column was used. on plates. After development, the plates were dried However, C8 column was used for determining in the air, and then viewed under 254 nm UV light. enalapril, trandolapril, lisinopril and quinapril. Then, densitometric measurements were made with Mobile phase used for cilazapril was phosphate wavelengths determined prior to analysis. buffer (pH = 2.75), tetrahydrofurane and triethyl- The regression curves were drawn for the ana- amine, for enalapril and trandolapril was phosphate lyzed compounds, determining their linearity in the buffer (pH = 2.0) and acetonitrile, for imidapril and following range: for lisinopril, quinapril and spi- moexipril ñ acetonitrile and water, for captopril, fos- rapril: 2.5 ñ 40 µg, for ramipril and trandolapril 5 ñ inopril and zofenopril ñ 0.1% phosphoric acid and 30 µg, for moexipril: 1 ñ 15 µg, for benazepril: 1 ñ methanol. A mobile phase consisting of acetonitrile, 20 µg, for cilazapril: 2 ñ 20 µg, for fosinopril: 2 ñ 40 methanol and phosphate buffer (pH = 3.0), was used µg, for captopril and enalapril: 5 ñ 50 µg, for imi- for lisinopril and quinapril; consisting of acetonitrile dapril: 2.5 ñ 20 µg and for zofenopril: 0.5 ñ 5 µg . and phosphate buffer (pH = 3.0) ñ for ramipril. For benazepril mobile phase consisting of phosphate Determination of the content in the analyzed stan- buffer (pH = 2.0) and methanol was used. Spirapril dards and pharmaceutical preparations was separated with a mobile phase consisting of Preparation of solutions tetramethylammonium hydroxide solution (pH = Methanol solutions were prepared for the ana- 2.4) acetonitrile and water. The results are presented lyzed substances and medicines at the standard con- in Tables 3 and 4. Identification and determination of antihypertonics from the group of angiotensin convertase inhibitors by... 141

Table 3. Statistical assessment of the results concerning the determination of the tested compounds in pharmaceutical substances. Arithmetic mean Standard Confidence brackets Tested Number of RSD Method of all measurements deviation X ± ∆X compound samples [%] X [%] S PU = 95%[%] Densitometric 6 99.12 0.76 99.12 ± 0.79 0.76 Lisinopril HPLC 6 101.45 1.11 101.45 ± 1.16 1.09 Densitometric 6 99.69 0.47 99.69 ± 0.50 0.47 Quinapril HPLC 6 101.67 1,02 101.67 ± 1.07 1.00 Densitometric 6 100.88 0.45 100.88 ± 0.47 0.44 Ramipril HPLC 6 100.80 0.17 100.88 ± 0.18 0.17 Densitometric 6 100.25 0.50 100.25 ± 0.53 0.50 Spirapril HPLC 6 100.03 0.23 100.03 ± 0.24 0.23 Densitometric 6 99.54 0.17 99.54 ± 0.18 0.17 Moexipril HPLC 6 100.10 0.18 100.10 ± 0.19 0.18 Densitometric 6 99.88 0.34 99.88 ± 0.36 0.34 Trandolapryl HPLC 6 99.32 0.33 99.32 ± 0.35 0.33 Densitometric 6 100.03 0.16 100.03 ± 0.17 0.16 Benazepril HPLC 6 98.73 0.48 99.73 ± 0.50 0.49 Densitometric 6 99.99 0.40 99.99 ± 0.40 0.40 Cilazapril HPLC 6 99.33 0.37 99.33 ± 0.37 0.37 Densitometric 6 100.00 0.38 100.00 ± 0.38 0.38 Fosinopril HPLC 6 100.08 0.40 100.08 ± 0.40 0.40 Densitometric 7 98.92 1.15 98.92 ± 1.06 1.16 Captopril HPLC 6 99.48 1.01 99.48 ± 1.06 1.01 Densitometric 6 99.15 1.07 99.15 ± 1.12 1.08 Enalapril HPLC 7 99.19 0.35 99.19 ± 0.32 0.35 Densitometric 6 99.37 0.39 99.37 ± 0.37 0.40 Imidapril HPLC 6 99.92 0.42 99.92 ± 0.40 0.43 Densitometric 6 99.76 0.26 99.76 ± 0.25 0.26 Zofenopril HPLC 6 99.47 0.31 99.47 ± 0.30 0.31

RESULTS AND DISCUSSION ues and detection limits are presented in Tables 1 and 2). By means of densitometric method it was pos- Automatic application in the process of determina- sible to specify the conditions of identification and tion performed by means of the densitometric method determination of all the investigated compounds allowed for a better precision of the method. It was pos- belonging to the group of angiotensin convertase sible to register the spectra of the standard, tested and inhibitors contained in the substances and medicines isolated substances and confirm their compatibility. (with the exception of perindopril, in case of which The following linearity was determined for: the trials of designing an appropriate mobile phase lisinopril, quinapril and spirapril: 2.5 ñ 40 µg, ended in failure). ramipril: 5 ñ 30 µg, moexipril: 1 ñ 15 µg, tran- After testing a number of mobile phases, it was dolapril: 5 ñ 30 µg, benazepril: 1 ñ 20 µg, cilazapril: possible to select the chromatographic patterns 2 ñ 20 µg, fosinopril: 2 ñ 40 µg, captopril and allowing for identification of the above mentioned enalapril: 5 ñ 50 µg, imidapril: 2.5 ñ 20 µg and compounds in the substances and medicines (Rf val- zofenopril: 0.5 ñ 5 µg. 142 ELØBIETA WYSZOMIRSKA et al.

Table 4. Statistical assessment of the results concerning the determination of the tested compounds in pharmaceutical products. Arithmetic mean Standard Confidence brackets Tested Number of RSD Method of all measurements deviation X ± ∆X compound samples [%] X [%] S PU = 95%[%] Lisinopril Densitometric 6 20.15 0.07 20.1 ± 0.07 0.34 tablets 20 mg HPLC 6 19.73 0.27 19.73 ± 0.28 1.38 Accupro 20 Densitometric 6 20.63 0.16 20.63 ± 0.17 0.78 tablets 20 mg HPLC 6 20.03 0.22 20.03 ± 0.23 1.08 Tritace 10 Densitometric 6 9.98 0.14 9.98 ± 0.15 1.44 tablets 10 mg HPLC 6 10.02 0.02 10.02 ± 0.02 0.24 Quadropril Densitometric 6 6.02 0.06 6.02 ± 0.06 1.02 tablets 6 mg HPLC 6 6.22 0.08 6.22 ± 0.08 1.26 Cardiotensin Densitometric 6 7.37 0.03 7.37 ± 0.03 0.41 tablets 7.5 mg HPLC 6 7.57 0.08 7.57 ± 0.08 1.00 Gopten Densitometric 6 2.08 0.02 2.08 ± 0.02 0.77 capsules 2 mg HPLC 6 1.94 0.03 1.94 ± 0.03 1.40 Lotensin Densitometric 6 10.03 0.06 10.03 ± 0.06 0.62 tablets 10 mg HPLC 6 9.92 0.06 9.02 ± 0.12 0.61 Inhibace Densitometric 6 1.05 0.01 1.05 ± 0.01 1.07 tablets 1 mg HPLC 6 1.08 0.01 1.08 ± 0.01 1.02 Monopril Densitometric 6 20.10 0.21 20.10 ± 0.21 1.05 tablets 20 mg HPLC 6 19.77 0.24 19.77 ± 0.24 1.23 Captopril Densitometric 7 12.71 0.13 12.71 ± 0.12 0.99 tablets 12.5 mg HPLC 7 12.88 0.10 12.88 ± 0.09 0.75 Enalapril Densitometric 7 19.96 0.18 19.96 ± 0.17 0.92 tablets 20 mg HPLC 6 20.81 0.07 20.81 ± 0.08 0.35 Tanatril Densitometric 6 19.44 0.20 19.44 ± 0.19 1.03 tablets 20 mg HPLC 6 19.60 0.06 19.60 ± 0.06 0.33 Zofenil Densitometric 6 29.95 0.17 29.95 ± 0.16 0.57 tablets 30 mg HPLC 6 30.08 0.22 30.08 ± 0.21 0.72

The respective equations were (correlation The determination limits were as follows: for coefficients in parantheses): captopril, enalapril, ramipril, trandolapril ñ 5 µg, for for lisinopril: y = 7309.5x + 15954 (0.9979), lisinopril, spirapril, imidapril and quinapril ñ 2.5 µg, for quinapril: y = 13912x + 30878 (0.9989), for moexipril, benazepril, cilazapril and fosinopril ñ for spirapril: y = 7552.3x + 78857 (0.9993), 1 µg, whereas for zofenopril ñ 0.5 µg. for ramipril: y = 7162.9x + 31351 (0.9992), The detection limits were as follows: for for moexipril: y = 7617x + 6110.1 (0.9980), ramipril and captopril 3.0 µg, for trandolapril 2 µg, for trandolapril: y = 7444.5x + 33286 (0.9986), for enalapril, lisinopril, spirapril and quinapril 1.0 for benazepril: y = 10289x + 15918 (0.9951), µg, for moexipril, cilazapril, imidapril and fosinopril for cilazapril: y = 6828.5x + 10878 (0.9960), 0.5 µg, for benazepril 0.2 µg and for zofenopril for fosinopril: y = 4481.5x + 84862 (0.9921), 0.025 µg. for captopril: y = 10833x + 6267.7 (0.9924), In order to make a comparison of the designed for enalapril: y = 9626.3x + 69729 (0.9911), method of the content determination in the tested for imidapril: y = 11961x + 20379 (0.9901) substances and medicines an analysis was per- and for zofenopril: y = 23673x + 13740 (0.9964). formed by means of HPLC method that is routinely Identification and determination of antihypertonics from the group of angiotensin convertase inhibitors by... 143 used for determining the content of tested com- 14. 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