Spectrophotometric and HPTLC-densitometric determination of lisinopril and hydrochlorothiazide in binary mixtures

Different spectrophotometric and HPTLC-densitometric methods are presented for the simultaneous determination of lisinopril and hydrochlorothiazide in pharmaceutical tablets. The spectrophotometric methods include third derivative (³D) ultraviolet spectrophotometry with zero crossing measurement at 217.4 and 233.4 nm, second derivative of the ratio spectra with measurement at 214.3 and 228.0 nm; both classical least squares and principal component regression were applied to the UV absorption and first derivative spectra of the mixture. The HPTLC method was based on separation of both drugs followed by densitometric measurements of their spots at 210 and 275 nm for lisinopril and hydrochlorothiazide, respectively. The separation was carried out on Merck HPTLC aluminum plates of silica gel 60 F₂₅₄, using chloroform–ethylacetate–acetic acid (10:3:2 by vol.) as mobile phase. The linear and second order polynomial were used for the regression equation of lisinopril and hydrochlorothiazide, respectively.     

A new spectrofluorimetric method for the determination of lisinopril in tablets

An accurate and precise spectrofluorimetric method is presented for the determination of lisinopril based on the formation of a derivative formed with 7-chloro-4-nitrobenzofurazan. The derivatization reaction proceeds quantitatively at pH 8.5-9.0 and 60 degrees C in 70 min when the molar ratio of reagent to the drug is 170. After the extraction with ethyl acetate the fluorescence intensity of the derivative was measured at 528 nm with excitation at 465 nm. Calibration graph is rectilinear over the range of 50-1000 ng/ml with detection and determination limits of 20 and 50 ng/ml, respectively. The regression equation is I(f) = 0.198C-0.299 (r = 0.9999). The method was applied to the commercially available tablets and the results were statistically compared with those obtained by official HPLC method.     

Spectrophotometric and LC determination of two binary mixtures containing antihistamins

Several methods are developed for the determination of two binary mixtures containing cyclizine hydrochloride with pyridoxine HCl (mixture (mix.) 1); and cinnarizine with piracetam (mix. 2). The resolution of the two binary mixtures has been accomplished by using numerical spectrophotometric methods as partial least squares (PLS-1) and principal component regression applied to UV spectra of the mixture and graphical spectrophotometric method as second derivative of the ratio spectra (2DD). In addition, HPLC methods were developed depending on using RP18 column with mobile phase consisting of acetonitrile/0.05 M KH2PO4 (50:50, v/v, pH 4.0) with UV detection at 239 nm for mix. 1, and mobile phase consisting of acetonitrile/0.05 M KH2PO4/triethylamine (50:50:0.2, v/v/v, pH 3.0) with UV detection at 227 nm for mix. 2. The proposed methods were successfully applied for the determination of the two binary combinations in synthetic mixtures and commercial tablets.     

Buccal absorption of enalapril and lisinopril

Objective: The buccal absorption of captopril does not exhibit the classical pH/partition hypothesis, suggesting that mechanisms other than passive diffusion are involved in its absorption; animal studies have suggested that a peptide carrier-mediated transport system may be responsible for its absorption. The present study evaluated the effects of pH on octanol partitioning, and on the buccal absorption of enalapril and lisinopril, using in vitro techniques and buccal partitioning in human volunteer subjects. Methods: The partitioning of enalapril and lisinopril into n-octanol was examined over the pH range of 3–9 at room temperature. Results: Enalapril exhibited maximal partitioning into the organic phase at pH 4–5; minimal partitioning was recorded at pH values 8 and 9. The partitioning of lisinopril into n-octanol was found to be maximal at pH 9 and minimal at pH 3. Using the buccal absorption technique, the partitioning of enalapril and lisinopril (0.5 mg), was examined in six healthy male volunteers from buffered solutions (pH 3, 4, 5, 6, 7, 8 and 9). In the case of enalapril, lowest buccal partitioning occurred at pH 3, 8 and 9, while maximal partitioning occurred at pH 5; absorption of lisinopril was not extensive at any pH, but was greatest at pH 6. These results, in addition to the n-octanol partition coefficients, indicated that enalapril obeyed the normal lipid partition hypothesis with respect to buccal absorption. The buccal absorption of lisinopril also obeyed the lipid partition hypothesis over the pH range 3–7. These findings are in direct contrast to those for captopril. The buccal partitioning experiments were repeated at the maximal pH for absorption for each angiotensin converting enzyme (ACE) inhibitor, but with the addition of cephradine (0.05 mmol · l⁻¹). Conclusion: The data indicated that the presence of this peptide transport inhibitor had no effect on the buccal absorption of enalapril (0.06 mmol · l⁻¹) and lisinopril (0.057 mmol · l⁻¹), which suggests that both drugs do not share a common buccal absorption pathway with cephradine. Received: 2 January 1998 / Accepted in revised form: 31 May 1998     

Spectrophotometric, spectrofluorimetric and LC determination of trazodone hydrochloride

Highly selective non-covalent clenbuterol (CL) imprinted polymers were prepared using methacrylic acid as monomer and ethylene glycol dimethacrylate as cross-linking agent. HPLC experiments with columns packed with this material showed that CL are selectively recognised with respect to all other adrenergic substances studied using a phosphate buffer/acetonitrile eluent. The separation was strongly dependent on pH and the organic/aqueous phase ratio. An important contribution to the recognition mechanism from hydrophobic interactions was found at higher water content. These results demonstrate that a novel family of absorbents with high selectivity for CL was obtained which can be exploited in solid phase extractions or as recognition elements for selective sensors.     

Identification of a new impurity in lisinopril

LC-UV scan of lisinopril revealed the presence of an unknown impurity (approximately 0.14%) at a relative retention time of 3.26 employing phosphate buffer-acetonitrile as binary gradient system while LC-MS analysis with binary gradient system comprising of a ammonia-ammonium acetate buffer (pH 5.0) and acetonitrile indicated it to be C31H41N3O7. The impurity was isolated by preparative HPLC utilizing a linear gradient of water and acetonitrile. The structural analysis of the isolated product by 1H, 13C NMR, mass spectroscopy and FT-IR revealed it to be a 4-phenyl butanoic acid derivative (CL) of lisinopril.     

Development and validation of a sensitive HPLC method for the determination of lisinopril in human plasma after derivatization with 4-fluoro-7-nitro-2,1,3-benzoxadiazole

In this study, we developed a simple and sensitive HPLC method for the determination of lisinopril in human plasma. The sample clean-up was carried out by solid-phase extraction (SPE) using a cation-exchange (Strata-SCX^®) extraction cartridge. After a pre-column derivatization with 4-fluoro-7-nitro-2,1,3-benzoxadiazole, the reaction mixture was analyzed on an Agilent Zorbax SB^®-C₁₈ (150 mm×4.6 mm, 5 μm). The flow rate was set at 1.0 mL/min. Fluorescence detection was performed at an excitation wavelength of 470 nm and an emission wavelength of 530 nm. The mobile phase consisted of a mixture of methanol and 0.02 M sodium dihydrogen phosphate (pH = 3.0, 60:40, v/v). The average extraction recovery of lisinopril and fluvoxamine (internal standard) was >85%. The method exhibited a linear calibration curve over the concentration range of 1–1000 ng/mL with a correlation coefficient (r²) of ≥0.98 and a limit of quantification (LOQ) equal to 2 ng/mL. The within-run and between-run precisions were satisfactory with an RSD of 3.8%–13.7% (accuracy: from 95.0% to 96.4%) and 4.273%–14.3% (accuracy: from 94.4% to 98.5%), respectively.     

Spectrophotometric and polarographic determination of enalapril and lisinopril using 2,4-dinitrofluorobenzene

The reaction of enalapril maleate and lisinopril with 2,4-dinitrofluorobenzene has been used to form colored products and polarographically active derivatives. The different experimental conditions have been optimized. The proposed methods have been validated and applied to the determination of both drugs in their commercial tablets. The results have been statistically compared with those obtained using the official HPLC methods.     

赖诺普利治疗急性心肌梗死38例

目的 :观察赖诺普利治疗急性心肌梗死的疗效。方法 :将73例心肌梗死患者随机分为治疗组38例 ,对照组35例 ;治疗组于心肌梗死后48小时内口服赖诺普利2.5mg,无低血压 ,则常规给药 ;其它治疗与对照组相同。结果 :心力衰竭发生率治疗组较对照组减少20.4% ,P<0.05 ,病死率两组差异无显著性。不良反应治疗组和对照组比较咳嗽差异有显著性 ,P<0.05 ,低血压发生率差异无显著性。结论 :赖诺普利可作为急性心肌梗死急性期减少心力衰竭的治疗方法之一。     

Effect of amlodipine,lisinopril and allopurinol on acetaminophen-induced hepatotoxicity in rats

BackgroundExposure to chemotherapeutic agents such as acetaminophen may lead to serious liver injury. Calcium deregulation, angiotensin II production and xanthine oxidase activity are suggested to play mechanistic roles in such injury.ObjectiveThis study evaluates the possible protective effects of the calcium channel blocker amlodipine, the angiotensin converting enzyme inhibitor lisinopril, and the xanthine oxidase inhibitor allopurinol against experimental acetaminophen-induced hepatotoxicity, aiming to understand its underlying hepatotoxic mechanisms.Material and methodsAnimals were allocated into a normal control group, a acetaminophen hepatotoxicity control group (receiving a single oral dose of acetaminophen; 750 mg/kg/day), and four treatment groups receive N-acetylcysteine (300 mg/kg/day; a reference standard), amlodipine (10 mg/kg/day), lisinopril (20 mg/kg/day) and allopurinol (50 mg/kg/day) orally for 14 consecutive days prior to acetaminophen administration. Evaluation of hepatotoxicity was performed by the assessment of hepatocyte integrity markers (serum transaminases), oxidative stress markers (hepatic malondialdehyde, glutathione and catalase), and inflammatory markers (hepatic myeloperoxidase and nitrate/nitrite), in addition to a histopathological study.ResultsRats pre-treated with amlodipine, lisinopril or allopurinol showed significantly lower serum transaminases, significantly lower hepatic malondialdehyde, myeloperoxidase and nitrate/nitrite, as well as significantly higher hepatic glutathione and catalase levels, compared with acetaminophen control rats. Serum transaminases were normalized in the lisinopril treatment group, while hepatic myeloperoxidase was normalized in the all treatment groups. Histopathological evaluation strongly supported the results of biochemical estimations.ConclusionAmlodipine, lisinopril or allopurinol can protect against acetaminophen-induced hepatotoxicity, showing mechanistic roles of calcium channels, angiotensin converting enzyme and xanthine oxidase enzyme in the pathogenesis of hepatotoxicity induced by acetaminophen.     

LC determination of enrofloxacin

A simple, rapid and sensitive high-performance liquid chromatographic (HPLC) method was developed for the assay of enrofloxacin in raw material and injection. The validation method yielded good results and included the range, linearity, precision, accuracy, specificity, recovery, limit of detection (LOD) and limit quantification (LOQ) values. The HPLC separation was carried out by reversed phase chromatography on a C-18 absorbosphere column (150×4.6 mm i.d. 5 μm particle size) with a phase composed of sodium acetate (pH 4.7; 0.1 M): acetonitrile (60:40, v/v; pH 5.0), pumped isocratically at a flow rate of 1.5 ml min⁻¹. The effluent was monitored at 278 nm with the eluting solvent. The calibration graph for enrofloxacin was linear from 10.0 to 80.0 μg ml⁻¹.     

赖诺普利联合羟苯磺酸钙治疗糖尿病肾病的临床观察

目的观察赖诺普利联合羟苯磺酸钙治疗糖尿病肾病的临床疗效及安全性。方法选择32例糖尿病肾病患者,随机分为实验组(18例)、对照组(14例)。对照组单用羟苯磺酸钙,实验组在此基础上加用赖诺普利。降糖药根据患者具体情况应用胰岛素皮下注射或口服降糖药治疗,各组疗程均为8周。疗程结束后检测并比较两组患者24 h尿白蛋白排泄率(24 h-UAER)、血肌酐(Scr)及尿素氮(BUN)等指标。结果实验组、对照组总有效率分别为94.5%、71.4%,差异有统计学意义(P<0.05)。治疗后,实验组的24 h-UAER、Scr、BUN较对照组下降明显(P<0.05)。结论赖诺普利联合羟苯磺酸钙治疗糖尿病肾病疗效确切,且无明显不良反应。     

Spectrophotometric determination of metronidazole and secnidazole in pharmaceutical preparations

A rapid and sensitive spectrophotometric method is proposed for determination of metronidazole and secnidazole. The method depends on the reduction of metronidazole and secnidazole molecule with zinc dust and hydrochloric acid flowed by diazotization and coupling with 8-quinolinol to give red colored chromogens easily measured spectrophotometrically which has λ_max = 500 nm. The experimental conditions were optimized and Berr's law was obeyed over the applicable concentration ranges both techniques were applied successfully to a wide variety of pharmaceutical preparations.     

硝酸甘油联合赖诺普利治疗顽固性心力衰竭疗效观察

目的 观察静脉滴注硝酸甘油联合口服赖诺普利治疗顽同性心力衰竭的疗效。方法46例符合标准的患者入选本研究。随机分为两组,治疗组在常规抗心力衰竭治疗的基础上加用静脉滴注硝酸甘油与口服赖诺普利;对照组给予常规抗心力衰竭治疗,疗程7～10d。观察两组的治疗效果。结果治疗组显效率为47．8％（11／23）．总有效率为86．9％（20／23）。对照组显效率为30-4％（7／23）,总有效率为69．6％（16／23）。治疗后两组疗效对比．显效率差异有统计学意义（P〈0．05）,总有效率差异有统计学意义（P〈0．05）。结论静脉滴注硝酸甘油联合口服赖诺普利治疗顽同性心力衰竭疗效显著,用药安全,不良反应少。     

A comparison of lisinopril and nifedipine in the treatment of mild to moderate hypertension

Lisinopril has been compared with slow-release nifedipine in a 16-week double-blind, randomized, parallel-group study involving 102 patients with mild to moderate hypertension. Sitting systolic and diastolic blood pressures were reduced 6 and 5 mm Hg more by lisinopril than by nifedipine over 12 weeks monotherapy.After 12 weeks a greater proportion of patients taking lisinopril was controlled (sitting diastolic blood pressure below 95 mm Hg) than in those taking nifedipine. As a result, 17% of those taking lisinopril and 38% of those taking nifedipine required additional therapy with hydrochlorothiazide. The addition of hydrochlorothiazide resulted in similar response rates in the lisinopril and nifedipine groups (89% and 75% respectively).The rate of reporting of adverse events considered to be drug-related and the rate of withdrawals were similar for both treatments. Cough was more often reported with lisinopril and headache, sweating, and hot flushes with nifedipine.We conclude that once-daily titrated doses of lisinopril produced better control of blood pressure than twicedaily titrated doses of nifedipine.     

Spectrophotometric determination of lisinopril in tablets using 1-fluoro-2,4-dinitrobenzene reagent

A spectrophotometric method for the determination of lisinopril (LN) in single and multicomponent tablets also containing hydrochlorothiazide (HCT), based on the derivatization reaction with 1-fluoro-2,4-dinitrobenzene (FDNB, Sanger reagent) is described. Aqueous solutions of LN (4.5-27.2 x 10(-5) M) react with FDNB (in acetonitrile) at pH 8.2 (borate buffer) in dark at 60 degrees C for 45 min. After acidification with HCl to decolourize 2,4-dinitrophenolate (the alkaline hydrolysis product of FDNB), the LN-derivative is measured at 356.5 or 405.5 nm (only at 405.5 nm if HCT is present). The calibration curves are linear (r>0.996 at both wavelengths) with a between days precision of slopes of 1.8 and 2.3% at 405.5 and 356.5 nm, respectively. The quantification limit is 3.49 x 10(-5) M (0.014 mg) at 405.5 nm and 5.69 x 10(-5) M (0.023 mg) at 356.5 nm. The accuracy and precision of the method were evaluated with the analysis of synthetic mixtures (Er%: 0.30-0.60 and 0.27-1.00 at 405.5 and 356.5 nm, respectively; RSD%: 0.48-0.92 and 0.35-0.51 at 405.5 and 356.5 nm, correspondingly; recovery%: 99.2-100.4 at 405.5 nm and 97.9-104.3 at 356.5 nm). Results obtained from the analysis of commercial preparations with the proposed method are in good agreement with those obtained with the official HPLC method (% relative difference 0.2-2.5%). The developed method can be used for rapid routine analysis for content uniformity, dissolution profile studies and assay of pharmaceutical preparations.     

Pharmacokinetics and pharmacodynamics of lisinopril in advanced renal failure

To prevent drug accumulation and adverse effects the dose of hydrophilic angiotensin-converting enzyme (ACE) inhibitors, e. g. lisinopril, must be reduced in patients with renal failure. To obtain a rational basis for dose recommendations, we undertook a prospective clinical trial. After 15 days of lisinopril treatment pharmacokinetic and pharmacodynamic parameters were determined in patients with advanced renal failure (n=8; endogenous creatinine clearance [CL_CR]: 18 ml·min^?1·1.73m^?2) and in healthy subjects with normal renal function (n=16; CL_CR: 107 ml·min^?1·1.73m^?2). The volunteers received 10 mg lisinopril once daily, the daily dose in patients (1.1–2.2 mg) was adjusted to the individual CL_CR according to the method of Dettli [13]. After 15 days of lisinopril treatment the mean maximal serum concentration (C _max) in patients was lower than in volunteers (30.7 vs 40.7 ng·ml^?1, while the mean area under the concentration-time curve (AUC _{0–24 h}) was higher (525 vs 473 ng·h^?1·ml^?1). ACE activity on day 15 was almost completely inhibited in both groups. Plasma renin activity, angiotensin I and angiotensin II levels documented marked inhibition of converting enzyme in volunteers and patients. Furthermore, average mean arterial blood pressure in patients decreased by 5 mmHg and proteinuria from 3.9–2.7 g per 24 h after 15 days of treatment with the reduced dose of lisinopril. Adjustment of the dose of lisinopril prevents significant accumulation of the drug in patients with advanced renal failure during chronic therapy. Mean serum levels did not exceed this in subjects with normal renal function receiving a standard dose. Despite substantial dose reduction, blood pressure and proteinuria decreases were observed.     

虎红、曲利本红-阿米卡星的光度法研究

在酸性条件下,硫酸阿米卡星(AMK)与虎红(TIR)、曲利本红(TRR)均可反应生成离子缔合物。在可见和近紫外区,TRR-AMK的最大显色波长位于392nm处,最大褪色波长位于350nm处,线性范围为0～16.0μg/ml(显色法)和0～14.0μg/ml(褪色法),表观摩尔吸光系数(ε)为1.50×104L/(mol·cm)(显色法)和5.54×103L/(mol·cm)(褪色法)。TIR-AMK使TIR溶液褪色,最大褪色波长位于538nm处,线性范围为0～16.3μg/ml,表观摩尔吸光系数(ε)为6.97×104L/(mol·cm)。它们在一定浓度范围内均遵从朗伯比尔定律,由此建立了测定硫酸阿米卡星的虎红、曲利本红光度法。该法用于市售药物及尿液中硫酸阿米卡星含量的测定,结果满意。     

A comparison of the effect of lisinopril and hydrochlorothiazide on electrolyte balance in essential hypertension

Summary The effects of lisinopril 10–20 mg or hydrochlorothiazide 25–50 mg (each given once daily) on blood pressure, serum sodium, potassium and magnesium concentrations, total body potassium and urinary cation excretion were compared in a group of hypertensive patients using a double blind randomised crossover design. Each active treatment phase lasted six weeks and a total of sixteen patients completed the study.Both lisinopril and hydrochlorothiazide produced clinically significant decreases in blood pressure. However, lisinopril treatment produced a mean reduction of 14 mm Hg in sitting diastolic pressure compared with a 7 mm Hg reduction for hydrochlorothiazide treatment. This difference was statistically significant. The decrease in the concentration of serum potassium during hydrochlorothiazide treatment was greater than that during lisinopril treatment (0.53 vs 0.01 mmol·l^–1). The absolute value of serum potassium was significantly lower on hydrochlorothiazide than on lisinopril therapy. Neither treatment had an effect on serum magnesium concentrations, nor was there any significant effect of either treatment on urine volume or urinary excretion of sodium, potassium or magnesium. There was a trend towards increased total body potassium concentration on lisinopril compared with a decrease in total body potassium on hydrochlorothiazide. However, this difference was just outside the range of statistical significance. Both treatments were equally well tolerated.The results indicate slight superiority of lisinopril over hydrochlorothiazide with regard to control of diastolic blood pressure with a better effect on overall electrolyte balance.