Low hematocrit and serum albumin concentrations underlie the overestimation of tacrolimus concentrations by microparticle enzyme immunoassay versus liquid chromatography-tandem mass spectrometry.
BACKGROUND
Rapid liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods are used increasingly for tacrolimus (TRL) monitoring but show a negative difference with respect to a microparticle immunoassay (MEIA). This report examines possible reasons for this difference between methods.


METHODS
We collected 1156 blood samples from 277 adult and 121 pediatric recipients of liver, renal, and bone marrow grafts or hepatocyte or pancreatic islet cell implants. TRL was measured in whole blood by MEIA and LC-MS/MS, and hematologic and biochemical data were collected when available.


RESULTS
LC-MS/MS was significantly more precise (P <0.02) than the MEIA with increased sensitivity. The MEIA had a median difference of 16.2% vs LC-MS/MS overall, and this was significantly affected by patient cohort (P <0.001). The difference was greater in adult or pediatric liver graft recipients while they were inpatients rather than outpatients (31.8% and 14.0% vs 7.5% and 6.5%, respectively). The difference was also greater in bone marrow than kidney graft recipients (32.8% vs 15.8%, respectively). Multiple linear regression analysis showed significant inverse relationships of this difference with hematocrit (packed cell volume) and plasma albumin (P <0.001) in the total cohort and a positive relationship with plasma bilirubin in a subgroup of pediatric liver graft recipients.


CONCLUSIONS
Patients with a low packed cell volume and plasma albumin are likely to show artificially high concentrations of TRL when measured by MEIA. The increased risk of underimmunosuppression must be considered should doses be reduced to lower these seemingly high TRL concentrations.
Brown
Nigel W
NW
Immunosuppressive Drug Monitoring, Institute of Liver Studies, King's College Hospital, London, UK. nigel.brown@kingsch.nhs.dk
Gonde
Christopher E
CE
Adams
Jemimah E
JE
Tredger
J Michael
JM
D000328:Adult; D016026:Bone Marrow Transplantation; D002648:Child; D002853:Chromatography, Liquid; D005189:False Positive Reactions; D006400:Hematocrit; D022781:Hepatocytes / Q000637:transplantation; D006801:Humans; D007124:Immunoenzyme Techniques; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000097:blood*; D016381:Islets of Langerhans Transplantation; D016030:Kidney Transplantation; D016031:Liver Transplantation; D013058:Mass Spectrometry; D010316:Particle Size; D012680:Sensitivity and Specificity; D012709:Serum Albumin / Q000032:analysis*; D016559:Tacrolimus / Q000008:administration & dosage / Q000097:blood*
D007166:Immunosuppressive Agents; D012709:Serum Albumin; D016559:Tacrolimus