Determination of aliskiren in human serum quantities by HPLC–tandem mass spectrometry appropriate for pediatric trials

Abstract

The orally active direct renin inhibitor aliskiren is approved for the treatment of essential hypertension in adults. Analytical methods utilized in clinical studies on efficacy and safety have not been fully described in the literature but need a large sample volume ranging from 200 to 700 μL, rendering them unsuitable particularly for pediatric applications. In the assay presented only 100 μL of serum is needed for mixed-mode solid-phase extraction. The chromatographic separation was performed on Xselect(TM) C18 CSH columns with mobile phase consisting of methanol-water-formic acid (75:25:0.005, v/v/v) and a flow rate of 0.4 mL/min. Running in positive electrospray ionization and multiple reaction monitoring the mass spectrometer was set to analyze precursor ion 552.2 m/z [M + H](+) to product ion 436.2 m/z during a total run time of 5 min. The method covers a linear calibration range of 0.146-1200 ng/mL. Intra-run and inter-run precisions were 0.4-7.2 and 0.6-12.9%. Mean recovery was at least 89%. Selectivity, accuracy and stability results comply with current European Medicines Agency and Food and Drug Administration guidelines. This successfully validated LC-MS/MS method with a wide linear calibration range requiring small serum amounts is suitable for pharmacokinetic investigations of aliskiren in pediatrics, adults and the elderly.

Liquid chromatography–tandem mass spectrometric assay for aliskiren, a novel renin inhibitor in micro‐volumes of human plasma: a pharmacokinetic application in healthy South Indian male subjects

“…The reported procedures (Burckhardt et al ., ) have employed solid‐phase extraction to extract aliskiren from human serum samples. Based on that, different sample pre‐treatment methods were investigated.…”

“…As per the literature, few analytical methods have been reported for the determination of aliskiren in biological samples, including liquid chromatography/mass spectrometric methods (Burckhardt et al ., ; Ayalasomayajula et al ., ; Dieterle et al ., ; Vaidyanathan et al ., ; Zhao et al ., ; Huang et al ., ; Limoges et al ., ) and high‐performance liquid chromatographic (HPLC) methods (Lefevre and Gauron, ). Most of the analytical methods reported so far were only for investigation of the pharmacokinetics properties of the drug.…”

“…Burckhardt et al . () reported an LC‐MS/MS method for the determination of aliskiren in human serum samples with the concentration range of 0.146–1200 ng/mL using 100 μL sample volume. This method employs multi‐step solid‐phase extraction involving many stringent method development protocols with a chromatographic run time of >5 min, which may not be favorable for routine subject analysis.…”

Development and validation of a HPLC‐PDA bioanalytical method for the simultaneous estimation of Aliskiren and Amlodipine in human plasma

“…Many UV and HPLC methods for quantitative and qualitative analysis of these drugs have been reported individually for ALS and AML (Anandakumar and Jayamariappan, ; Bhatia et al ., ; Chitlange et al ., ; Dongre et al ., ; Feng et al ., ; Jothieswari et al ., ; Kumar, ; Mohammadi et al ., ; Nalwade et al ., ; Patil et al ., ; Rathee et al ., ; Salve et al ., ; Wrasse‐Sangoi et al ., ). However, an intensive literature search revealed the bioanalytical methods reported for determination of ALS (Adireddy et al ., ; Aydoğmuş et al ., ; Burckhardt et al ., ; Limoges et al ., ; Waldmeier et al ., ), AML (Bahrami and Mirzaeei, ; Bhatt et al ., ; Ma et al ., ; Tatar and Atmaca, ; Zarghi et al ., ), a combination of AML and HCTZ (El‐Gizawy et al ., ; Sharma and Pancholi, ) and a combination of ALS and HCTZ (Belal et al ., ). To the best of our knowledge there is no bioanalytical method available for the simultaneous determination of ALS and AML.…”

Tailored Assays for Pharmacokinetic and Pharmacodynamic Investigations of Aliskiren and Enalapril in Children: An Application in Serum, Urine, and Saliva

“…10 Therefore, a tailored method that required only 0.1 mL serum per sample was successfully developed to reliably determine aliskiren concentration. 11 The second investigated antihypertensive drug was enalapril, an ACEI. Enalapril is administered as a prodrug with a bioavailability of about 50% to 60% and is subsequently converted by hepatic carboxylesterases (CES1) to its active metabolite, enalaprilat.…”