Determination of amlodipine, indapamide and perindopril in human plasma by a novel LC–MS/MS method: Application to a bioequivalence study

Abstract

A robust and rapid UPLC–MS/MS method has been developed, optimized and validated for determination of amlodipine (AML), indapamide (IND) and perindopril (PRN) in human plasma. A positive electrospray ionization mode was used in a Xevo TQD LC–MS/MS instrument. A single sample preparation step using extraction technique was applied to extract the three analytes from plasma samples. There was no need to extract indapamide from blood samples in a further step. Extraction of the three drugs and internal standards was done using a solvent mixture composed of methyl tertiary butyl ether, dichloromethane and ethyl acetate. The prepared samples were analyzed using an Acquity UPLC HSS C18 (100 × 2.1 mm, 1.7 μm) column. Ammonium acetate and methanol, pumped at a flow rate of 0.3 ml/min, were used as a mobile phase. Method validation was done as per the US Food and Drug Administration guidelines. Linearity was achieved in the range of 0.2–15 ng/ml for AML, 0.5–50 ng/ml for IND and 0.5–120 ng/ml for PRN. Accuracy and precision were estimated and found to be within the acceptable ranges. The rapid chromatography permits analysis of many samples per batch, making the method suitable for clinical and pharmacokinetic investigations. The developed and validated method was applied to estimate AML, IND, and PRN in a fasting bioequivalence study in healthy human volunteers.

Potential pharmacokinetic interactions in fixed-dose combinations of perindopril/indapamide/amlodipine compared with perindopril/indapamide and amlodipine in healthy Chinese volunteers

“…Oral administration of S06593 (perindopril arginine salt 5 mg/indapamide 1.25 mg/amlodipine 5 mg) and S05590 (perindopril tert-butylamine salt 4 mg/ indapamide 1.25 mg) or amlodipine 5 mg in healthy Chinese volunteers led to similar mean plasma concentration-time profiles for perindopril, perindoprilat, indapamide and amlodipine. Another bioequivalence study has also shown no drug-drug interactions among perindopril, indapamide and amlodipine in healthy participants administered a FDC of perindopril/indapamide/ amlodipine [45].…”

Chromatographic methods and approaches for bioequivalence study, drug screening and enantioseparation of indapamide

“…It was observed that (i) there was poor recovery of Indp from plasma samples so it could be quantified only in blood samples in high concentrations [25,32,36] and not in plasma, and (ii) the new formulation containing three APIs (namely, amlodipine, Indp and perindopril) was being used for treatment of high blood pressure due to arterial hypertension [38]. Considering this literature, Rezk and Badr in 2020 [39] described quantitation of Indp in plasma collected from six batches of 26 Egyptian individual adult volunteers. Methyl t-butyl ether-dichloromethane-ethyl acetate (40:40:20, v/v) was used to extract the APIs by LLE approach in one step (with a recovery of >91%).…”

Spectrofluorimetric assay of amlodipine and perindopril in their raw materials, pharmaceutical formulations and spiked human plasma through the formation of complexes with Eosin Y

“…1-a). Various analytical techniques have been reported for determination of AML, either alone or in combination with other drugs, including, spectrophotometric techniques (Attimarad et al 2019;Erden et al 2016;Hegazy et al 2015;Karadurmuş et al 2018;Khachornsakkul and Dungchai 2020;Mahant et al 2016;Saad et al 2016;Siridevi et al 2019), spectrofluorimetric techniques (Attala et al 2020;Dinç et al 2017;El-Kosasy et al 2015;Ibrahim et al 2015;Mabrouk et al 2018;Mohamed et al 2016;Mohammed 2015;Nasr and Shalan 2020;Sh Shalan et al 2015;Shereen Shalan and Nasr 2019), electrochemical techniques (Erden et al 2016;Wei et al 2016) and chromatographic techniques such as TLC-densitometry (Patel et al 2020a, b), LC-MS/ MS (Rezk and Badr 2020) and HPLC (Alaama et al 2015;Attimarad et al 2020;Desai et al 2019;Duraisamy and Jaganathan 2017;Ebeid et al 2015;Karadurmuş et al 2018;Mahant et al 2016;Nagamani et al 2020;Naik et al 2020;Patel et al Patel et al 2020a, b;Saleh et al 2020;Saputri et al 2018). Perindopril (PER), is an antihypertensive nonsulfhydryl angiotensin converting enzyme (ACE) inhibitor used to treat hypertension and stable coronary artery disease with nomenclature of (2S,3aS,7aS)-1-[(2S)-2-[[(2S)-1-ethoxy-1-oxopentan-2-yl]amino]propanoyl]-2,3,3a,4,5,6,7,7a-octahydroindole-2-carboxylic acid (Fig.…”

“…1-b). For determination of PER alone or in combination, a variety of analytical techniques have been reported including spectrophotometric techniques (El-Bagary et al 2016;Hegazy et al 2015;Karadurmuş et al 2018;Magdy et al 2018;Rahman et al 2017;Saad et al 2016;Siridevi et al 2019), spectrofluorimetric techniques (Al-Haj Sakur et al 2015Fael and Sakur 2015a, b;Sakur et al 2015) and chromatographic techniques including TLC-densitometry (Patel et al 2020a, b), LC-MS/MS (Rezk and Badr 2020) and HPLC (Duraisamy and Jaganathan 2017;Hassan et al 2020;Hemdan et al 2018;Karadurmuş et al 2018;Naik et al 2020;Patel et al 2020a, b;Saleh et al 2020).…”