RML  provides research and therapeutic drug monitoring analysis for the new anti-rejection and anti-proliferative drugs Sirolimus (Rapamycin),  everolimus (Certican), tacrolimus (FK-506), cyclosporine (CyA), Temsirolimus, Mycophenolic acid (MPA) and other immuno-suppressants and anti-proliferatives using state-of-the-art technology.  In particular, we employ HPLC/MS/MS for clinical biosamples and HPLC/UV or HPLC/PDA for raw and formulated materials.  We analyze these compounds in whole blood, solid tissues and raw materials.  Because rapamycin, tacrolimus, and everolimus are macrolide biotechnology products,  there are significant analytical concerns with respect to stability and purity.  These compounds have many interesting analytical characteristics which may require more extensive HPLC and HPLC/MS/MS work than is normal for routine clinical assays.

We have extensive experience in the analysis of the large number of degradants that form from these entities. Please call to discuss your analytical needs.  Rapamycin, tacrolimus, temsirolimus, and everolimus may be quite unstable in certain environments and formulations.

Sirolimus and everolimus are anti-rejection medications often used in conjunction with cyclosporine, tacrolimus, mycophenolate, ascomycin, and other agents for the avoidance of organ rejection following transplantation.  As for many other therapeutic agents, therapeutic monitoring is considered to be useful as an aid to therapy.  Unlike the situation for many other drugs, there are few adequate immunoassays available.  The immunoassays that are available often suffer from non-specificity.   

Rapamycin, tacrolimus, and similar compounds may be present in more than one form.  Our analysis includes, when appropriate, the measurement of metabolites and degradants of these substances. 

Sirolimus and analogs, such as everolimus, are being used experimentally for the treatment of many other conditions.  We can provide cGLP analyses of blood and tissue for such projects.

We are CLIA registered and actively participate in proficiency testing.  If your facility would like to consider having RMIL provide immunosuppressant analysis services, please contact either Dr. Patricia Sulik or Dr. Robert Lantz at RMIL.   Please note that we work ONLY with transplant centers, pharmaceutical companies,  and researchers.  We do not accept samples directly from patients.

We have found that LC Labs is a very good source of the above products.
 

We offer TDM and clinical trials assays for other less-common therapeutic agents, such as Taxol  (paclitaxel),  doxorubicin, epirubicin, and the toxic AZT metabolite (AMT).  We are cGLP compliant.  We have a long list of analytes for which we have valid assays.

REFERENCES:

1.    Rapamune Product Monograph  Wyeth-Ayerst Laboratories, St. Davids, PA.

2.    "Advances in Therapeutic Drug Monitoring for Immunosuppressants: A Review of Sirolimus"  Clinical Therapeutics  22, Suppl. B, (2000).

3.     Holt, DW, Lee, T, Jones, K, and Johnston, A, "Validation of an Assay for the Routine Monitoring of Sirolimus using HPLC with Mass Spectrometric Detection"   Clinical Chem. 46 (8) 1179-1183  (2000).

4.    Taylor, PJ, Johnson, AG,   "Quantitative Analysis of Sirolimus (Rapamycin) in Blood by High Performance Liquid Chromatography-Electrospray Tandem Mass Spectrometry" J. Chrom. 718 251-7 (1998).

5.    Zhou, C., Stewart, KD, and Dhaon, M. "An intramolecular ionic hydrogen bond stabilizes a cis-amide bond rotamer of a ring-opened rapamycin-degradation product." Magnetic Resonance in Chemistry 43, 41-46 (2004). 
 

Rocky Mountain Instrumental Laboratories, Inc.
108 Coronado Ct.
Ft. Collins, CO  80525

970-266-8108
 

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LAST UPDATE:   16 APRIL 2012