Small Molecule Bioanalysis

KCAS Bio has more than a 40-year history in the Small Molecule Bioanalysis area. Traditionally focusing on LC-MS/MS approaches, in the last 10 years we have added several other platforms including ligand binding assays to support small molecule bioanalysis.

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Small molecule bioanalysis, cutting-edge techniques

Our highly experienced scientists use the appropriate state-of-the-art technologies and instrumentation to support all small molecule bioanalysis from Discovery to Clinical in compliance with non-GLP and GLP regulations as needed. KCAS Bio scientists focus on thorough method development to provide robust assays for qualification, validation and sample analysis. Our laboratories have the latest instrumentation to provide ultimate sensitivity and effectively measure drug (PK), metabolite and biomarker (PD) concentrations in biological matrices, such as plasma, serum, cerebrospinal fluid (CSF), urine and tissues.

Small Molecule Bioanalysis at KCAS Bio refers to the bioanalysis of any molecule or modality with a molecular weight of less than 10K Daltons. These would include some of the more common ones such as:

• Traditional small molecule drugs (Lipinski rule of five)
• Amino Acids
• Peptides (linear, cyclic, branched, conjugated etc.)
• Oligos (siRNA, antisense oligonucleotides, peptide nucleic acids, Morpholino analogues)
• Lipid Nanoparticle embedded analytes (LNP)
• Lipids (glycosphingolipids (GSL), ceramides, sphingolipids, gangliosides)
• Steroids
• Polypeptides & small proteins (insulin, GLP-1)
• Acylated peptides (GLP-1 analogues and other polypeptides)
• Toxins (Payloads from ADCs)


LC-MS/MS is typically the gold standard technology used for the Bioanalysis of Small Molecules (both for Pharmacokinetics or Pharmacodynamics) in drug discovery, preclinical, and clinical studies, including bioanalysis of drugs and metabolites, biomarkers, and active endogenous compounds in biological fluids and tissues, from non-GLP to GLP. At KCAS Bio, we use appropriate sample preparation techniques as needed such as protein precipitation (PPT), solid phase extraction (SPE), and liquid extraction (LLE).

Hybrid or traditional LC-MS/MS provides an ideal complement to the more established ligand-binding approaches. At KCAS Bio, we partner with our clients to identify the analytical approach to best answer their questions.

Liquid Chromatography Mass Spectrometry

Ligand Binding Assays

Ligand Binding Assays can also be used to support small molecule bioanalysis. Typically, LBA might be used more for biomarkers than PK due to the limited availability of various commercial reagents. Examples include assays for quantitation of various eicosanoids or leukotrienes.

KCAS Bio has extensive experience using LBA technologies to support small molecule projects.

Ligand Binding Assays

Small molecule projects

Some of the projects include work in the following, from non-GLP to GLP: 

  • Small Molecule Drugs 
  • Oligonucleotide / Nucleotides / Oligonucleotide Analogs (e.g. Morpholino)siRNA by both LC-MSMS and Fluorescent tagged LC-FL, Anti-sense Oligonucleotides (ASOs), Peptide nucleic acids (PNAs) 
  • Peptides – GLP-1, GIP, exenatide, semaglutide, liraglutide, etc.   
  • Eicosanoids – Prostaglandins, leukotrienes, thromboxanes, HETEs, ETEs, etc. 
  • Amino Acid panels – 20 common and several other uncommon in various tissues and fluids 
  • Metabolites
  • Other Biomarkers (Nicotinamide adenine dinucleotide (NAD), adenosine triphosphate (ATP), short and long chain fatty acids, phospholipids, saturated and unsaturated fatty acids, steroids, organometallics)  
  • Unstable Molecules with limited solution or matrix stability 
  • Lipid Analysis 
    • GSLs – ceramides, sphingosines, Mono, di, tri -hexosylceramides, hexosylsphingosines, gangliosides 
    • Lipid analysis LNPs – Liquid Nanoparticle Embedded Analytes

Small molecule expertise

Expertise in analytical approaches for small molecules include:

  • Hydrophilic Interaction Chromatography (HILIC) 
  • Solid phase extraction (SPE), Liquid-Liquid Extraction (LLE), Supported Liquid Extraction (SLE) 
  • Derivatizations 
  • Fast PK / Screening with the focus more on the profile trends 
  • PK/ TK / Extended Studies with focus on actual parameter absolute values 
  • Protein Binding (Rapid Equilibrium Dialysis or RED, and BioSPME) 
  • Size Exclusion Chromatography (SEC) 
  • Matrices – all fluids and all tissue types 
  • Micro Sampling (Volumetric absorptive microsampling or VAMS) 
  • HRMS 

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