Comparative pharmacokinetics of trandolapril, its active metabolite, and verapamil in human plasma of Egyptian population using HPLC–MS/MS

Abstract

Trandolapril and verapamil are commonly used antihypertensive drugs. However, there is a lack of available data on the change of their pharmacokinetics in patients with liver or kidney impairment and hence the need for dose adjustment. In this article, a high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method was developed and validated for the monitoring of trandolapril, its active metabolite trandolaprilat, and verapamil in human plasma of patients with renal impairment and/or liver insufficiency. The chromatographic separation was achieved on a Gemini C reversed phase column using a gradient elution mode with a run time of 10 minutes. The mobile phase consisted of a mixture of methanol and 2% acetic acid. The electrospray ionization MS/MS analysis was performed in multiple reaction monitoring (MRM) mode. The assay was validated as per Food and Drug Administration (FDA) guidelines for bioanalytical method validation and proved to be suitable for the determination of therapeutic drug levels in plasma. The inter-group changes in pharmacokinetic data were compared to that of healthy volunteers. The comparison showed a significant difference in the pharmacokinetic parameters between the studied groups. The presented results exhibit the benefits of the proposed assay as a validated analytical tool for the continuous drug monitoring.

Simultaneous spectrophotometric determination of drugs lacking peak maxima in their zero-order profiles by graphical or statistical representation of data

“…Several reported chromatographic methods were found for determination of the mixture. Also, two different colorimetric methods were found for the mixture [16,17]. But during the literature survey, there were no direct spectrophotometric methods for determination of Trandolapril and Verapamil combination.…”

“…TR/VER`* VER` = TR (16) After that we divide the obtained spectra by a normalized spectrum divisor of TR. So, the constant obtained in the plateau region which shown in Figure 6 is related to TR concentration.…”

“…Many methods were reported for the analysis of this combination or one of its components in pharmaceuticals or body fluids. These include spectrophotometry [10], HPLC with spectrophotometric detection [11,12], high performance thin layer chromatography [13,14] and LC-MS/MS [15,16]. In 2014, Vijayalakshmi et al suggested a colorimetric method for determination of Trandolapril and Flucloxacillin in pharmaceutical formulation, where the Trandolapril color complex was measured at 430 nm [17].…”

Development and validation of first and zero order derivative spectrophotometric methods for the determination of rilmenidine in pharmaceutical preparations and forced degradation study

“…[1][2][3][4][5][6][7] Today, there are various drug treatment classifications used in the treatment of hypertension, commonly referred to as antihypertensive drugs. [8][9][10][11] Antihypertensive drugs were categorized into six separate drug groups: Angiotensin converting enzyme (ACE)-inhibitors, Angiotensin-receptor blockers (ATR-blockers), diuretics, beta-blockers, calciumchannel blockers and other antihypertensive drugs. [12] Rilmenidine is an antihypertensive agent with selectivity for I1 imidazoline receptors that acts both centrally by reducing sympathetic overactivity and in the kidney by inhibiting the Na + /H + antiport.…”