iC42 Services

https://medschool.cuanschutz.edu/ic42toxicology

Comprehensive Urine Drug Testing

Where our validated assay detects and confirms the presence of prescription, illicit and over the counter drugs in urine. With the use of mass spectrometer and high performance liquid chromatography systems (HPLC-MS/MS), our methods can quantify 136 compounds in a single test.

CAP and CLIA accredited, HIPPA Compliant

Participation in CAP proficiency testing:

• UT – Urine Toxicology
• DMPM – Drug Monitoring for Pain Management
• ETB – Ethanol Biomarkers

PASSED most recent inspection/audit by CAP in November 2016

Guidance used for Method Validation

• College of American Pathologists checklist,
• “Method Validation for Industry Bio-analytical Method
  

Complete Validation of Assay

Pediatric Pharmacological Solutions/
Dried Blood Spots (DBS)

The iC42 laboratory has developed and validated an LC-MS/MS assay to quantify the following in dried human whole blood spots (DBS):

• Morphine and metabolites
• Fentanyl and metabolites
• Acetaminophen
• Ketamine
• Bupivicaine
  

DBS Method

Our DBS method of analysis generally achieves quantitation levels from 1 – 1000 ng/mL. Only 50 μL of human whole blood is required to be placed onto a specified dried blood patch. A specific size portion of the whole blood patch is extracted and injected onto a LC-MS/MS system. This sampling technique allows for whole blood sampling from infants, finger sticks, and low volume animal models (such as mice). The assay may also be easily adapted for testing of other small molecules.

iC42 offers a range of drug metabolism services (please see below). These studies are carried out in compliance with applicable FDA guidances following the “fit for purpose” principle.

These include:

• In vitro drug metabolism studies
• Identification of metabolite structures
• Generation and isolation of pure metabolites
• Quantification of metabolites drug metabolites in animal toxicokinetic studies
• Quantification of drug metabolites in clinical trials and pharmacokinetics
• Clinical drug-drug interaction studies
• Pediatric drug metabolism

Generation and isolation of pure metabolites

Using state of the art preparatory HPLC we separate and purify metabolites which have been custom synthesized in our laboratory. Metabolites are synthesized using microsomes, hepatocytes, and bacteria. We currently have methods for many of the immunosuppressant drugs along with many other small molecule compounds. In most cases we can promise a two week delivery of high purity metabolite compounds. 

In vitro drug metabolism services:

(I) Interspecies Comparison of In Vitro Metabolism: Metabolic profiling of different species using liver slices, hepatocytes and microsomes, cytochrome P450 phenotyping, cytochrome P450 inhibition, and cytochrome P450 induction, and if necessary, metabolism by hepatic cytosol, hepatic mitochondrial fractions and evaluation of phase II metabolism.
(II) Metabolic Pathway Identification (Reaction Phenotyping): Identification of cytochrome P450 and other enzymes involved in metabolism of new medications using expressed isolated cytochrome P450 and/or other drug metabolizing enzymes, specific inhibitory antibody and specific chemical inhibitors.
(III) Cytochrome P450 Inhibition: Estimation of apparent inhibition constants (Ki) and half-maximal inhibition constants (IC50) values.
(IV) Induction of cytochrome P450 enzymes: Evaluation of the potential induction of cytochromes by a new compound.
(V) Metabolite Identification: Isolation of drug metabolites, identification of metabolite structures using mass spectrometry and NMR spectroscopy, development and validation of LC/MS, LC/MS/MS or GC/MS assays for quantification of parent drugs and metabolites in blood and tissues, analysis of study samples from pharmacokinetic studies.
(VI) Metabolite stability: Metabolism of a new medication using hepatic microsomes or hepatocytes from a variety of species for metabolite stability and estimate of intrinsic clearance (Clint).
(VII) In vitro permeability studies: Determine the intestinal permeability and/or blood-brain barrier permeability of new compounds.
The investigators have extensive experience and expertise in the field of drug metabolism, analytics, pharmacokinetics, toxicology, and FDA drug approval procedures. Our laboratory is CAP accredited, and cGLP compliant and has a full DEA license as well as an accredited animal facility.

For an overview about the typical strategic approach for Drug Metabolism Studies for a New Drug Candidate, please click here. 

For a list of purified and certified immunosuppressant metabolites please click here.

For an overview of other offered metabolites please click here.