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HPTLC method development and validation of trandolapril in bulk and pharmaceutical dosage forms

April 2010
Journal of Advanced Pharmaceutical Technology & Research 1(2):172-9

DOI:10.4103/2231-4040.72255

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PubMed

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CC BY-NC-SA 3.0

Authors:

Sreekanth Nama. Dr

Rescisco Global Regulatory Consultants

Bahlul Zayed Awen

University of Tripoli

CH BABU RAO

University of Zawia

A simple, precise, accurate and rapid high performance thin layer chromatographic method has been developed and completely validated for the estimation of trandolapril in bulk and pharmaceutical dosage forms. Quantification of trandolapril was carried out with percolated silica gel 60F(254) as stationary phase using mobile phase consisting of Chloroform: Methanol: Acetic acid (8:1.5:0.5 v/ v/ v) and scanned in Absorbancei Reflectance mode at 212 nm using Camag TLC scanner 3 with WinCAT software. The R(f) value of trandolapril was found to be 0.54 (±0.03). The proposed method has permitted the quantification of trandolapril over the linearity range of 25-150 ng/spot and its percentage recovery was found to 99.7%. The intraday and inter day precision were found to be 1.26% and 1.4%, respectively. The limit of detection and the limit of quantification were found to be 18 ng/ spot and 54 ng/ spot, respectively. The proposed method can be successfully applied for the estimation of drug content of different marketed formulations simultaneously on a single plate and provides a faster and cost effective quality control tool for routine analysis of trandolapril as bulk drug and in tablet dosage forms.

Chemical structure of trandolapril

…

A typical Densitogram of Trandolapril

…

Linearity of Trandolapril

…

Precision of Trandolapril

…

Intra-day precision of Trandolapril

…

Figures - uploaded by Sreekanth Nama. Dr

Content may be subject to copyright.

Content uploaded by Sreekanth Nama. Dr

Content may be subject to copyright.

J. Adv. Pharm. Tech. Res. Vol. 1 (2), Apr-Jun, 2010 ISSN 0976-2094

172

HPTLC METHOD DEVELOPMENT AND VALIDATION OF TRANDOLAPRIL IN BULK

AND PHARMACEUTICAL DOSAGE FORMS

N. Sreekanth

, Bahlul Z.Awen

, Ch. Babu Rao

1. Department of Pharmacy, College of Public Health and Medical sciences, Jimma

University, Jimma, (Ethiopia)

2. Faculty of Pharmacy, 7

April University, Zawia, (Libya)

Corresponding Author’s E-mail: - sreekanthpharma@yahoo.co.in

Received: 01

April 2010 Revised: 28

May 2010 Accepted: 06

June 2010

ABSTRACT

A simple, precise, accurate and rapid high performance thin layer chromatographic

method has been developed and completely validated for the estimation of trandolapril

in bulk and pharmaceutical dosage forms. Quantification of trandolapril was carried

out with percolated silica gel 60F

254

as stationary phase using mobile phase consisting

of Chloroform: Methanol: Acetic acid (8:1.5:0.5 v/v/v) and scanned in

Absorbance/Reflectance mode at 212 nm using Camag TLC scanner 3 with WinCAT

software. The R

value of trandolapril was found to be 0.54 (±0.03). The proposed

method has permitted the quantification of trandolapril over the linearity range of 25-

150 ng/spot and its percentage recovery was found to 99.7%. The intra day and inter

day precision were found to be 1.26% and 1.4%, respectively. The limit of detection and

the limit of quantification were found to be 18 ng/spot and 54 ng/spot, respectively.

The proposed method can be successfully applied for the estimation of drug content of

different marketed formulations simultaneously on a single plate and provides a faster

and cost effective quality control tool for routine analysis of trandolapril as bulk drug

and in tablet dosage forms.

Key words: HPTLC, Validation, Trandolapril.

INTRODUCTION

Trandolapril, chemically, it is (2S, 3aR,

7aS)-1-[(S)-N-[(S)-1-carboxy-3-

phenylpropyl] alanyl] hexahydro-2-

indolinecarboxylic acid, 1-ethyl ester [1]

and is not official in any

pharmacopoeia. The chemical structure

of trandolapril was shown in Fig. 1.

Trandolapril is a nonsulphydryl prodrug

that is hydrolysed to the active diacid

trandolaprila. Trandolapril is an orally

administered angiotensin converting

enzyme inhibitor that has been used in

the treatment of patients with

hypertension and congestive heart

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173

failure, and myocardial infarction [2-3].

Literature survey revealed that few

HPLC methods were reported for the

estimation of trandolapril in the

biological fluids [4-10]. The present

study illustrates development and

validation [11] of a simple, accurate,

precise and specific HPTLC method for

the estimation of trandolapril tablet

dosage forms.

Fig. 1: Chemical structure of

trandolapril

EXPERIMENTAL

Reagents

Pure working standard of trandolapril

was procured as a gift sample from

Ranbaxy Ltd., Himachal Pradesh. All

chemicals and reagents used were of

analytical grade. A Silica gel 60F

254

TLC

pre coated aluminum plates (10×10 cm,

layer thickness 0.2 mm, E. Merck,

Mumbai) were used as a stationary

phase. Chloroform: Methanol: Acetic

acid (8:1.5:0.5 v/v/v) was used as

mobile phase and methanol was used

as solvent. Commercially available

Tablet formulations with labeled

amount 2.0 mg of trandolapril (Zetpril-

2, Hetero Drugs Pvt. Ltd. and Mavik-2,

Abott Pharmaceuticals Ltd) were

purchased from the local market.

Apparatus

A CAMAG HPTLC system (Switzerland)

comprising a CAMAG Linomat IV

semiautomatic sample applicator, a

CAMAG TLC Scanner 3, A CAMAG twin-

trough chamber (10 × 10 cm), CAMAG

CATS 4 software, A Hamilton syringe

(100 µl), A Shimadzu libror AEG-220

weighing balance and A ultra sonicator

(Frontline FS-4, Mumbai) was used

during the study.

Chromatographic conditions

The chromatographic conditions were

optimized and estimations were

performed on a stationary phase, pre

coated silica gel 60 F

254

aluminum

sheets (10×10 cm) which were pre-

washed with methanol and dried in air,

with mobile phase of Chloroform:

Methanol: Acetic acid (8:1.5:0.5 v/v/v) .

The chromatographic chamber and

plate was allowed to saturate for about

30 min and the migration distance

allowed was 72 mm. The wavelength

scanning was performed at 212 nm

keeping the slit dimension 5×0.45 mm.

The source of radiation was deuterium

lamp emitting a continuous UV

spectrum between 190-400nm. The

standard solutions of trandolapril was

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174

spotted and developed at constant

temperature of 25 ± 2ºC.

Preparation of mobile phase

Chloroform: Methanol: Acetic acid

(8:1.5:0.5 v/v/v) was employed as

mobile phase.

Preparation of standard solution of

trandolapril

A working standard of trandolapril

about 2.5 mg was accurately weighed

and transferred in to 100 ml volumetric

flask. A volume of methanol about 25

ml was added and sonicated for about

20 min; finally the volume was made up

to 100ml with methanol to obtain the

concentration about 25 µg/ml. From

this stock solution 0.1 ml was taken

and the volume made up to 100ml to

get concentration about 25ng/ml.

Preparation of calibration curve

Aliquots (1, 2, 3, 4, 5 and 6 µl) of

standard solution of trandolapril were

spotted on pre coated TLC plates using

semi automatic spotter under nitrogen

stream. The plate was dried in air and

developed up to 72 mm at constant

temperature with a mixture of

Chloroform: Methanol: Acetic acid

(8:1.5:0.5 v/v/v) as mobile phase in a

CAMAG twin through chamber which

was previously saturated with mobile

phase for about 30 min. the plate was

removed from the chamber and dried in

air. Photometric measurements were

performed at 212 nm in

absorbance/reflectance mode with the

CAMAG TLC scanner 3 using CATS 4

software incorporating track optimizing

option. The standard plot of trandolapril

was established by plotting the peak

area Vs concentration (ng/ml)

corresponding to each spot.

Estimation of trandolapril in

marketed tablet formulation

Twenty tablets were accurately weighed

and finely powdered. The powder which

is equivalent to 2.5 mg of trandolapril

was weighed, mixed with 25 ml of

methanol and sonicated for 15 min. The

solution of tablet was filtered through

Whatman filter paper No. 41 and the

residue was thoroughly washed with

methanol. The filtrate and washings

were combined in a 100 ml volumetric

flask and diluted to the mark with the

methanol to get the final concentration

of 25 µg/ml of trandolapril. From this

stock solution 0.1 ml was taken and the

volume made up to 100ml to get

concentration about 25ng/ml. Three

micro liters of sample solution was

applied on a TLC plate under a nitrogen

stream using a semi automatic spotter.

The amount of trandolapril present in

the sample solution was determined by

fitting the area values of peaks

corresponding to trandolapril into the

equation of the line representing the

J. Adv. Pharm. Tech. Res. Vol. 1 (2), Apr-Jun, 2010 ISSN 0976-2094

175

calibration curve of trandolapril. All

determinations were performed in

triplicate.

RESULTS AND DISCUSSION

Method development

Trandolapril was soluble in methanol,

there fore methanol was selected as the

solvent. A solvent system consisting of

Chloroform: Methanol: Acetic acid

(8:1.5:0.5 v/v/v) was selected as mobile

phase, that would give dense and

compact spot with appropriate R

values

was selected for quantification of

Trandolapril in pharmaceutical

formulations. The present HPTLC

method for the quantification

trandolapril in bulk and pharmaceutical

dosage, revealed as simple, accurate

and precise with R

value of 0.54. The

typical densitogram of trandolapril was

shown in Fig.2.

Fig. 2: A typical Densitogram of

Trandolapril

Validation of method

The Linearity for the detection of

trandolapril was 25-150 ng/ml with R

0.998; Y=21.07x + 21.71. The results

were shown in the Table-1. The

precision of the method (System

reproducibility) was assessed by

spotting 3 µl of drug solution six times

on a TLC plate, followed by development

of plate and recording the peak area for

6 spots. The % RSD for peak area

values of trandolapril was found to be

1.04%. The results were shown in

Table-2a. The method reproducibility

(The intra-day precision) was

determined by analyzing standard

solutions in the concentration range of

75 ng/spot to 100 ng/spot of drug for 3

times on the same day and inter-day

precision was determined by analyzing

corresponding standards daily for 3 day

over a period of one week. The intra-day

and inter-day coefficients of variation

(%RSD) are in range of 0.39 to 1.26 and

0.17 to 1.4, respectively. The results

were shown in Table-2b, 2c. Recovery

studies were carried out to assess

accuracy of the method. These studies

were carried out at three levels. The

percentage recovery was found to be

within the limits and shown in Table-3.

The assay for the marketed formulation

was established with the present

chromatographic conditions developed

and it was found to be more accurate

and reliable. The average drug content

was found to be 99.15% of the labeled

J. Adv. Pharm. Tech. Res. Vol. 1 (2), Apr-Jun, 2010 ISSN 0976-2094

176

claim. The results were shown in Table-

4. Limits of Detection (LOD) and

Quantification (LOQ), the limits of

detection and quantitation were

calculated by the method based on the

standard deviation of response (σ) and

the slope of calibration plot (S), using

the formulae LOD = 3.3σ/S and LOQ =

10σ/S. The LOD and LOQ were

calculated and found to be 18 ng/Spot

and 54 ng/Spot, respectively.

Robustness was determined by altering

chromatographic conditions like mobile

phase composition, Amount of mobile

phase, Plate treatment, Time from

spotting to chromatography and time

from chromatography. The low value of

% RSD indicates robustness of the

method. The results were shown in the

Table-5. Specificity test of the proposed

method demonstrated that there were

no interference form excipients.

Furthermore, well shaped peaks

indicate the specificity of the method.

Table 1: Linearity of Trandolapril

No.

Track

No.

Concentration

(ng/Spot) Area

A2 A3 Mean Peak Area

±SD

1 1 25 550.13

610.0 560.25 573.46±32.04

2 2 50 1079.6

1029.05 1076.53

1061.66±28.29

3 3 75 1595.1

1609.73 1565.0 1589.94±22.8

4 4 100 2110.0

2150.25 2175.25

2145.16±32.9

5 5 125 2709.1

2720.25 2729.25

2719.25±10.09

6 6 150 3100.6

3116.5 3157.63

3124.91±29.43

Table 2a: Precision of Trandolapril

S. No. Concentration (ng/spot) Peak area

1595.1

1609.73

1566.00

1575.43

1598.05

1585.34

Mean Peak Area ± SD -1528.66± 15.95; %RSD- 1.04

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177

INTRA-DAY PRECISION

Table 2b: Intra-day precision of Trandolapril

S. No. Concentration (ng/spot) Area Mean S.D % RSD

1 1575.4

2 75 1615.9 1595.366667 20.25594563 1.26

3 1594.8

1 2715.7

2 100 2729.4 2717.85 10.6391964 0.39

3 2708.45

1 3145.65

2 125 3105.6 3123.583333 20.33484284 0.65

3 3119.5

INTER-DAY PRECISION

Table 2c: Inter-day precision of Trandolapril

S. No. Concentration

(ng/Spot) Area Mean S.D % RSD

1 1565.28

2 75 1608.5 1589.993333 22.26845602 1.4

3 1596.2

1 2705.69

2 100 2715.24 2710.496667 4.775314998 0.17

3 2710.56

1 3154.36

2 125 3110.6 3130.586667 22.12438775 0.7

3 3126.8

Table 3: Recovery studies of Trandolapril

No.

Amount Present (mg)

(A)

Amount added (mg)

(B) A+B Amount found %Recovery

1 2.0 8.0 10.0 9.92 99.2

2 2.0 10.0 12.0 11.93 99.4

3 2.0 12.0 14.0 13.96 99.7

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Table 4: Assay of Trandolapril

S. No. Label claim (mg/tablet) Amount of drug estimated* (mg) % Purity %RSD

1 2.0 1.983 99.15 0.13

*Mean of three values

Table 5: Robustness of Trandolapril

S. No. Parameter %RSD Mean %RSD

(n=3)

100

(n=3)

125

(n=3)

1. Mobile phase Composition 0.56 0.48 0.32 0.45

2. Amount of mobile phase 0.31 0.63 0.45 0.46

3. Plate treatment 0.35 0.26 0.47 0.36

4. Time from spotting to chromatography

0.54

0.33 0.57 0.48

5. Time from chromatography to scanning 0.61 0.46 0.59 0.55

CONCLUSION

The developed HPTLC technique is

simple, precise, specific and accurate

and the statistical analysis proved that

method is reproducible and selective for

the analysis of trandolapril in bulk and

pharmaceutical formulations.

ACKNOWLEDGEMENT

The authors are thankful to Department

of Pharmacy, College of Public Health

and Medical sciences, Jimma

University, Jimma, Ethiopia and

authors greatly acknowledge Ranbaxy

Ltd., Himachal Pradesh for providing

the gift sample of Trandolapril.

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CURR PHARM ANAL

Background Hispidulin, a flavonoid renowned for its diverse pharmacological activities, is abundant in S. barbata D. Don. Given its prevalence, it is essential to establish a dependable analytical method for quantifying hispidulin in this plant. Methods This study introduces a sensitive and reliable high-performance thin-layer chromatographic (HPTLC) method for both qualitative and quantitative analysis of hispidulin in S. barbata D. Don. Pre-coated TLC aluminum plates were utilized, and after testing various mobile phase combinations, the most effective separation was achieved with Toluene-ethyl acetate-formic acid (5:4:1, v/v/v). The method underwent extensive validation for linearity, specification, instrument precision, precision, limits of LOD and LOQ, accuracy, and robustness. Results The developed method demonstrated excellent linearity over a specified concentration range, with a determination coefficient (r2) of 0.988. A well-defined spot at Rf 0.7, corresponding to hispidulin, was observed. The concentration of hispidulin in the hydroethanolic extract of S. barbata D. Don was quantified as 13.02 μg/mg of extract. Conclusion In conclusion, the HPTLC method presented in this study offers a simple, accurate, and robust tool for quantitatively analyzing hispidulin in the hydroethanol extract of S. barbata D. Don. This method is suitable for routine quality control and standardization of herbal formulations containing S. barbata D. Don, thereby contributing to the advancement of research in natural product- based pharmaceuticals.

Stability Indicating Derivative Spectrophotometric Method for Determination of Trandolapril in Bulk and in Formulation

Article

Jan 2024

AN IMPROVED LC-MS/MS METHOD DEVELOPMENT AND VALIDATION FOR THE DETERMINATION OF TRANDOLAPRIL AND VERAPAMIL IN HUMAN PLASMA

Article

Feb 2019

Objective: A simple, sensitive and rapid LC-MS/MS technique was developed for the quantitation of trandolapril (TDL) and verapamil (VPL) in a biological matrix and validated. Methods: Sample preparation processed by SPE (Solid Phase extraction) on phenomenex cartridge using Ledipasvir as an internal standard. Two drugs were eluted on waters symmetry-RP18 (5µ, 150 mm×4.0 mm) column with the mobile composition of 10 mmol ammonium formate and ACN(acetonitrile) in the ratio of 70:30 %V/V. Detection and quantitation were processed by electrospray ionization in positive ionization mode. Results: The quantification approach was validated in 5-1500 ng/ml linear concentration range for TDL and 1-2000 ng/ml for VPL. The intraday and inter-day precision and accuracy were found to be 0.58% to 5.69% and 93% to 104% for two drugs. The average recoveries for TDL and VPL were found to be 92.9% and 93.5% respectively. Conclusion: The developed work was validated and can be applicable to the routine analysis of TDL and VPL simultaneously in a biological matrix.

Identification and Process Development for enhanced Production of Lipstatin from Streptomyces toxytricini (Nrrl 15443) and furtherDownstream Processing

Article

Jan 2012

The selected strain Streptomyces toxytricini (NRRL 15443) was evaluated for production of an anti-obesity drug, Lipstatin. The study includes the optimization of seed media and using Plackett-Burman method for Production fermentation media for increasing the yield of the strain selected. Two extraction methods were used for comparative study followed by purification on silica gel column and identification of lipstatin molecule using sophisticated techniques such as IR, NMR, and mass spectroscopy. The presence and identification was also confirmed .

Development and validation of a liquid chromatographic method for the determination of trandolapril and verapamil in capsules

Article

Jun 2007

The development and validation of an isocratic high performance liquid chromatographic procedure for the determination of trandolapril and verapamil in capsules is reported. The drugs were analysed on a LiChrosorb RP18 column with a mobile phase composed of acetonitrile-methanol-phosphate buffer pH 2.7 (40:40:20) and UV detection at 220 nm. Peak height ratios were linearly related to amounts of the drugs in the range 4–20 μg/mL.The inter-day precision (CV) obtained for the standard solutions ranged from 0.40 to 2.18% for trandolapril and from 0.35 to 2.57% for verapamil. The inter-day coefficients of variation for replicate analyses in capsules ranged from 0.5 to 2.49% for trandolapril and from 0.33 to 1.61% for verapamil.The recovery of analytes after extraction from formulations using the described method, was 99.94 ± 1.69% and 98.13 ± 1.20% (mean ± SD) for trandolapril and verapamil, respectively.

Liquid chromatographic tandem mass spectrometric determination of trandolapril in human plasma

Article

Jun 2005
ANAL CHIM ACTA

A liquid chromatographic tandem mass spectrometric method for the determination of trandolapril in human plasma has been developed and fully validated. The article describes, in detail, the bioanalytical procedure and summarizes the validation results obtained. The samples were extracted using HLB Oasis solid-phase extraction cartridges. The chromatographic separation was performed on X-Terra C8 MS column (150 mm × 4.6 mm i.d., 5 μm particle size) using a mobile phase consisting of acetic acid 20 mM and triethylamine 4.3 mM/acetonitrile (40:60 (v/v)), pumped isocratically at 0.35 ml/min.The analytes were detected using a micromass quattro micro triple quadrupole mass spectrometer with positive electrospray ionization in multiple reaction-monitoring (MRM) mode. Tandem mass spectrometric detection enabled the quantitation of trandolapril down to 2.0 ng/ml. Calibration graphs were linear (r better than 0.996, n = 9) in the concentration ranges 2.0–750 ng/ml and the intra- and inter-day R.S.D. values were less than 3.83 and 3.86% for trandolapril.

Analysis of ACE inhibitors in pharmaceutical dosage forms by derivative UV spectroscopy and liquid chromatography (HPLC)

Article

Dec 1997
J PHARMACEUT BIOMED

Derivative UV spectroscopy and high performance liquid chromatography (HPLC) were applied to the determination of angiotensin-converting enzyme (ACE) inhibitors in their pharmaceutical dosage forms. For spectrophotometric determinations, the more appropriate derivative order was selected for each drug: ramipril (third-order), benazepril (second-order), enalapril maleate (second-order), lisinopril (first- and second-order) and quinapril (first-order). Reverse phase HPLC procedures (ODS column) were developed able to provide a single, symmetric peak for each drug; mixtures A-B, where A is 20 mM sodium heptansulphonate (pH 2.5) and B is acetonitrile-THF (95:5 v/v), proved to be suitable mobile phases to obtain selective separations of the cited ACE inhibitors. At ambient temperature, a low pH value (2.5) was found to be critical to avoid peak splitting and band broadening.

Trandolapril: An update of its pharmacology and therapeutic use in cardiovascular disorders

Article

Dec 1998

Unlabelled: Trandolapril is an orally administered angiotensin converting enzyme (ACE) inhibitor that has been used in the treatment of patients with hypertension and congestive heart failure (CHF), and after myocardial infarction (MI). Trandolapril is a nonsulfhydryl prodrug that is hydrolysed to the active diacid trandolaprilat. Trandolapril 2 mg once daily provides effective control of blood pressure (BP) over 24 hours in patients with mild to moderate hypertension, with a trough/peak ratio of BP reduction (as determined by 24-hour ambulatory monitoring) consistently > or = 50%. Trandolapril has similar antihypertensive efficacy to enalapril as indicated by several clinical trials. Combined therapy with trandolapril and sustained-release verapamil has a significantly greater antihypertensive effect than either agent alone. Only limited data are available on the use of trandolapril in patients with CHF, although ACE inhibitors as a class are recommended as first line therapy in such patients. In the Trandolapril Cardiac Evaluation (TRACE) study, trandolapril 1 to 4 mg once daily resulted in an early and long term reduction in all-cause mortality, including cardiovascular mortality, in patients with left ventricular (LV) dysfunction after an MI. Trandolapril therapy was commenced a mean 4.5 days after acute MI and continued for 24 to 50 months. At study end, the relative risk of death from any cause with trandolapril versus placebo was 0.78 (p = 0.001). The tolerability profile of trandolapril is similar to that of other ACE inhibitors. Most adverse events are mild and transient in nature, and include cough, asthenia, dizziness, headache and nausea. Trandolapril has no adverse effect on lipid or carbohydrate metabolism. Conclusions: trandolapril has a favourable pharmacological profile and an antihypertensive efficacy at least comparable to that of other ACE inhibitors. The pharmacological characteristics of trandolapril allow it to provide good 24-hour control of BP with once-daily administration. Trandolapril has also demonstrated some efficacy in a small number of patients with CHF. In addition, trandolapril provides long term protection against all-cause mortality in patients with LV dysfunction after MI. The results of the Prevention of Events with Angiotensin Converting Enzyme Inhibition (PEACE) study will determine its potential as a cardioprotective agent in patients with coronary artery disease and preserved LV function. Thus, trandolapril represents an effective, well-tolerated and convenient treatment option for patients with mild to moderate hypertension or LV systolic dysfunction after MI.

Trandolapril Reduces the Incidence of Atrial Fibrillation After Acute Myocardial Infarction in Patients With Left Ventricular Dysfunction

Article

Aug 1999
CIRCULATION

Studies have suggested that ACE inhibitors have an antiarrhythmic effect on ventricular arrhythmias. Whether they have an effect on atrial fibrillation is unknown. We investigated the effect of ACE inhibition with trandolapril on the incidence of atrial fibrillation in patients with reduced left ventricular function secondary to acute myocardial infarction. The patients in this study were those who qualified for inclusion into the TRAndolapril Cardiac Evaluation (TRACE) study, a randomized double-blind placebo-controlled study and who had sinus rhythm on the ECG obtained at randomization. Patients who fulfilled the criteria for inclusion were randomized to treatment with the ACE inhibitor trandolapril or placebo and were followed up for 2 to 4 years. Development and time to occurrence of atrial fibrillation in one 12-lead ECG recorded at the outpatient visits was the primary end point of this investigation. Of the 1749 patients included in the TRACE study, 1577 had sinus rhythm on the ECG recorded at randomization. Of these patients, 790 were randomized to trandolapril treatment and 787 to placebo treatment. The groups differed only slightly with respect to baseline characteristics. A total of 64 patients developed atrial fibrillation during the 2- to 4-year follow-up period. Significantly more patients developed atrial fibrillation in the placebo group than in the trandolapril group, 5.3% (n=42) versus 2.8% (n=22), respectively, P<0.05. Cox multivariable regression analysis, adjusting for important baseline characteristics, revealed that trandolapril treatment significantly reduced the risk of developing atrial fibrillation (RR, 0.45; 95% CI, 0.26 to 0.76; P<0.01). The results from the present study demonstrate that trandolapril treatment reduces the incidence of atrial fibrillation in patients with left ventricular dysfunction after acute myocardial infarction.

High-performance liquid chromatographic assay of trandolapril in capsules

Article

Nov 1999
ACTA POL PHARM

Rapid, simple and accurate chromatographic (HPLC) method for the determination of trandolapril was elaborated. Samples were chromatographed on a LiChrosorb RP-18 column and the mobile phase was acetonitrile -0.067 M phosphate buffer pH 2.7 (7:3, v/v). The UV detection at 220 nm and benazepril as an internal standard were used. The method was tested for linearity (over the range 4-20 micrograms.ml-1), precision and accuracy and was successfully applied for the quantitative determination of trandolapril in capsules.

A study on the stereochemical purity of trandolapril and octahydro-1 H-indole-2-carboxylic acid by HPLC method

Article

Nov 2002
ACTA POL PHARM

HPLC conditions for the identification of stereoisomers and stereochemical purity of the key intermediate in Trandolapril synthesis, octahydro-1H-indole-2-carboxylic acid, and final drug were elaborated. The chemical and stereochemical purity of synthetic Trandolapril was proved to be as high as 99.3-99.8%, on both non chiral and chiral RP-columns.

Quantification of trandolapril and its metabolite trandolaprilat in human plasma by liquid chromatography/tandem mass spectrometry using solid-phase extraction

Article

Dec 2006

A sensitive high-performance liquid chromatography/electrospray ionization tandem mass spectrometry (MS/MS) method was developed and validated for the simultaneous quantification of trandolapril and its metabolite trandolaprilat in human plasma using ramipril as an internal standard. Following solid-phase extraction, the analytes were separated using an isocratic mobile phase on a reversed-phase column and analyzed by MS/MS in the multiple reaction monitoring mode using the respective [M-H]- ions, m/z 429/168 for trandolapril, m/z 401/168 for trandolaprilat and m/z 415/166 for the internal standard. The method exhibited a linear dynamic range of 20-10,000 pg/mL for both trandolapril and trandolaprilat in human plasma. The lower limit of quantification was 20 pg/mL for both trandolapril and its metabolite. Acceptable precision and accuracy were obtained for concentrations over the standard curve range. A run time of 2.0 min for each sample made it possible to analyze more than 400 human plasma samples per day. The validated method has been successfully used to analyze human plasma samples for application in pharmacokinetic, bioavailability or bioequivalence studies.

Simultaneous Determination of Perindopril, Indapamide, Ramipril, Trandolapril in Pharmaceutical formulations using Reverse Phase Liquid Chromatography

Jan 2003
144-154

J.N. Harlikar
A.M. Amlani

HPTLC method development and validation of trandolapril in bulk and pharmaceutical dosage forms

Abstract and Figures

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