MSACL 2019 EU Abstract

LC-MS/MS Method for Screening of Intoxication and Drug Adherence of Angiotensin Converting Enzyme Inhibitors in Plasma

Mohsin Ali, Stephanie Laeer, Bjoern B Burckhardt
Institute of clinical pharmacy and pharmacotherapy, Heinrich Heine university Duessledorf, Germany

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Mohsin Ali (Presenter) Institute of Clinical Pharmacy and Pharmacotherapy >> POSTER (PDF)

Presenter Bio: I originally belong to Pakistan. After completion of my M.Phil in pharmacology, I am doing my PhD at the institute of clinical pharmacy and pharmacotherapy in Bioanalysis as major. I have used LC-MS/MS for the quantitative and qualitative analysis of small molecules.

Relevant Financial Disclosures (within past 24 months) Grant/Research Support MSACL Trainee grant support Conflict mitigation NOT REQUIRED.

BACKGROUND
Angiotensin converting enzyme inhibitors (ACEIs) are used for the treatment of cardiovascular diseases. The therapeutic effectiveness of these preventive agents is closely related to medication adherence by patients. Additionally, the increased availability of these drugs has led to the increased events of intoxication either intentionally or unintentionally. Qualitative screening of these agents using liquid chromatography-tandem mass spectrometry (LC-MS/MS) represents a reliable technique for monitoring medication adherence as well as intoxication.
OBJECTIVE
The objective was to develop a qualitative screening method for commonly prescribed angiotensin converting enzyme inhibitors in residual blood volume.
METHODS
Oasis® mix mode anion exchange (MAX) 96 well plate was used for solid phase extraction (SPE) to achieve sophisticated sample preparation. The LC-MS/MS (Shimadzu LC.10; Sciex, API 2000) in positive ion mode was performed using X-select CSH™ C18 analytical column. A gradient elution was used consisting of acetonitrile and water (both featuring 1% formic acid and 2 mM ammonium formate) as the mobile phase with a total run time of 10 minutes at 0.4mL/min. Fit-for-purpose method validation for semi-quantitative screening method was applied for following parameters: accuracy and precision, limit of detection (LOD), recovery and matrix effect.
RESULTS
The linearity ranged from 0.78-100 ng/mL covering typical plasma drug concentration levels in adults after daily dosing. The calibration curve was linear with co-efficient of correlation value (r ≥ 0.995) for all analytes except for perindopril (r=0.993). The method exhibited sensitivity with the LOD ranged from 0.41 to 0.65 ng/mL making its applicability in paediatric patients having a risk of severe side effects even with very low drug concentration due to inappropriate administration or unintentional intoxication. Inter-day accuracy and precision for low quality control level was within ±20% (80.98 to 108.71%) and (1.98 to 11.79%) respectively. At middle and high quality control level, inter-day accuracy was ±15% ranged from 90.06 to 109.64%. Inter-day precision ranged from 2.55 to 14.93% at middle and high quality control levels. Only perindopril and trandolapril slightly deviated in inter-day precision at low quality control levels (21.59 and 22.84%). The obtained recoveries were ≥ 87% and absolute matrix effect ranged from 100 to 113%. The method showed good repeatability for all analytes (1.9 to 15.8%).
CONCLUSION
The screening method was successfully developed and validated qualitatively for monitoring of medication adherence and intoxication of 10 ACEIs in 50 μL residual blood samples.
DISCLOSURE
The results presented here have already been published in BIOANALYSIS VOL. 10, NO. 23 and permission was duly obtained from the journal editor to present the contents as a poster on congress.