Ranolazine-d8 2HCl | CAS 142387-99-3

Ranolazine-d8 2HCl is a stable isotope-labeled analogue of ranolazine, in which eight hydrogen atoms are replaced with deuterium (²H or D). It is primarily used as an internal standard (IS) for quantitative LC-MS/MS analysis of ranolazine in biological matrices, pharmaceutical formulations, pharmacokinetic studies, bioequivalence testing, and therapeutic drug monitoring. Because the labeled compound possesses nearly identical physicochemical and chromatographic properties to the native analyte while remaining distinguishable by mass spectrometry, it provides highly accurate and reproducible quantification by compensating for extraction losses, ion suppression, and instrument variability. Stable isotope-labeled reference standards such as Ranolazine-d8 2HCl are widely employed in regulated bioanalytical laboratories following FDA, ICH, and EMA guidance for quantitative mass spectrometric assays.

Ranolazine is an anti-anginal pharmaceutical indicated for the treatment of chronic stable angina. Analytical methods supporting its development, bioavailability assessment, generic drug development, and pharmacokinetic evaluation require a reliable isotopically labeled internal standard to ensure high analytical accuracy across complex biological samples. Ranolazine-d8 2HCl fulfills this requirement by closely matching the extraction efficiency, chromatographic retention, and ionization characteristics of the unlabeled compound while producing a unique mass transition during tandem mass spectrometry analysis.

Chemical Properties of Ranolazine-d8 2HCl

The following section is suitable for a product page on ResolveMass Laboratories Inc.

Applications of Ranolazine-d8 2HCl

Ranolazine-d8 2HCl has broad utility throughout pharmaceutical research and regulated analytical laboratories. Common applications include:

• LC-MS/MS quantitative bioanalysis
• Pharmacokinetic (PK) studies
• Bioavailability and bioequivalence (BA/BE) studies
• Clinical bioanalytical assays
• Therapeutic drug monitoring
• Drug metabolism and disposition studies
• Method development and validation
• Generic drug development
• Pharmaceutical quality control
• Stability studies
• Forensic and toxicological investigations
• Research involving cardiovascular therapeutics

Its isotopic labeling enables precise correction for analytical variability, making it the preferred internal standard in validated quantitative methods.

Importance in LC-MS/MS Quantification

Modern bioanalytical assays demand exceptional sensitivity and reproducibility, particularly when measuring drugs at trace concentrations in plasma, serum, or urine. Matrix effects arising from endogenous biological components frequently influence ionization efficiency, resulting in inaccurate quantification if appropriate internal standards are not used.

Ranolazine-d8 2HCl effectively compensates for these analytical challenges because it behaves almost identically to the native analyte during:

• Sample extraction
• Protein precipitation
• Solid-phase extraction (SPE)
• Liquid-liquid extraction (LLE)
• Chromatographic separation
• Electrospray ionization
• Mass spectrometric detection

Since only the molecular mass differs due to deuterium incorporation, both compounds experience nearly identical analytical conditions, significantly improving assay precision, recovery, and accuracy.

Benefits of Using a Stable Isotope-Labeled Internal Standard

Compared with structural analogues or surrogate standards, Ranolazine-d8 2HCl offers several analytical advantages:

• Superior quantitative accuracy
• Improved assay precision
• Excellent correction for matrix effects
• Compensation for extraction variability
• Reduced analytical bias
• Enhanced reproducibility between analytical runs
• Increased confidence in regulatory submissions
• Improved robustness during method validation
• Better long-term assay performance

These advantages make isotope-labeled standards indispensable for regulated bioanalytical laboratories operating under GLP, GMP, or GCP environments.

Pharmaceutical Research Applications

Ranolazine-d8 2HCl supports numerous stages of pharmaceutical drug development, including:

Bioanalytical Method Development

During LC-MS/MS method development, the labeled internal standard assists scientists in optimizing chromatographic separation, determining appropriate mass transitions, evaluating recovery, minimizing matrix effects, and improving overall assay robustness.

Pharmacokinetic Studies

Clinical pharmacokinetic investigations require precise measurement of drug concentrations across multiple time points. Ranolazine-d8 2HCl provides reliable normalization throughout sample preparation and instrument analysis, resulting in dependable concentration-time profiles.

Bioequivalence Studies

Generic drug manufacturers rely on validated bioanalytical methods to demonstrate equivalence between reference and test products. Stable isotope-labeled internal standards improve assay reproducibility and support compliance with global regulatory expectations.

Clinical Research

Clinical laboratories utilize Ranolazine-d8 2HCl to accurately quantify ranolazine concentrations in human plasma and other biological matrices during Phase I through Phase IV clinical studies.

Role in Regulatory Bioanalysis

International regulatory agencies emphasize the importance of robust internal standards in quantitative bioanalysis. Stable isotope-labeled compounds are considered the preferred choice because they closely mimic the analytical behavior of the target analyte.

The use of Ranolazine-d8 2HCl supports analytical methods developed in accordance with:

• FDA Bioanalytical Method Validation Guidance
• ICH M10 Bioanalytical Method Validation Guideline
• EMA Bioanalytical Method Validation Guideline

These regulatory frameworks require demonstration of assay accuracy, precision, selectivity, recovery, matrix effect evaluation, and stability, all of which benefit from the use of an isotope-labeled internal standard.

Typical Analytical Workflow

A validated LC-MS/MS assay utilizing Ranolazine-d8 2HCl generally follows these steps:

1. Addition of the internal standard to biological samples.
2. Sample preparation using protein precipitation, SPE, or liquid-liquid extraction.
3. Chromatographic separation by reversed-phase HPLC or UHPLC.
4. Detection using tandem mass spectrometry operating in multiple reaction monitoring (MRM) mode.
5. Quantification based on analyte-to-internal standard peak area ratios.
6. Data processing using validated calibration curves and quality control samples.

This workflow delivers highly reproducible quantitative data suitable for regulated pharmaceutical research.

Quality Considerations

For reliable quantitative analysis, laboratories typically select isotope-labeled reference standards that provide:

• High isotopic enrichment
• Excellent chemical purity
• High isotopic purity
• Batch-to-batch consistency
• Long-term stability under recommended storage conditions
• Comprehensive analytical documentation, including COA and characterization data

High-quality reference materials help minimize analytical variability and improve confidence in reported results.

Why Choose ResolveMass Laboratories?

ResolveMass Laboratories Inc. supplies high-quality stable isotope-labeled reference standards designed to support pharmaceutical research, bioanalysis, and analytical method development. Our expertise in mass spectrometry, isotope-labeled compounds, and regulated analytical services enables researchers to achieve reliable and reproducible quantitative results.

We support pharmaceutical, biotechnology, CRO, CDMO, and academic laboratories with products suitable for:

• LC-MS/MS assay development
• Method validation
• Pharmacokinetic studies
• Bioequivalence studies
• Clinical research
• Drug metabolism investigations
• Quality control laboratories
• Regulatory submissions

Our commitment to scientific quality, analytical excellence, and customer support makes ResolveMass Laboratories a trusted partner for stable isotope-labeled reference standards.

 

Learn more about Deuterated Chemicals through,

• Deuterated Polymers: A Cornerstone Guide to Synthesis, Applications, and Future Trends
• Availability of All the Deuterated Chemicals at ResolveMass Laboratories Inc. 
• ResolveMass Laboratories: Leading Deuterated Chemical Synthesis Company in the United States.
• Deuterated Internal Standards for LC-MS: Selection & Custom Synthesis 
• How to Choose the Right Deuterated Labelled Chemical Synthesis Company in Canada 
• How to Choose the Right Deuterium Labelled Compounds Supplier for Your Lab 
• Deuterium-Labelled Compounds — Synthesis, Applications & Ordering 
• Custom Synthesis of Deuterated Chemicals