August 2011 Clinical Laboratory News: Cross Reactivity of Tacrolimus and Sirolimus Major Metabolites

American Association for Clinical Chemistry

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Table 1 Cross Reactivity of Cyclosporine Major Metabolites
Metabolite	Bioactivity (%)	Concentration Relative to Parent (%)	Seimens ACMIA	Seimens ADVIA	Microgenics CEDIA	Roche EMIT	Syva EMIT	Abbott MEIA
AM1 (M17) 1-β-hydroxyl	10–20	80–150	1.8% @ 1000 ng/mL	<5% @ 1000 ng/mL	4.4% @ 1000 ng/mL	<AS @ 500 ng/mL	<0.3% @ 500 ng/mL -5.9% @ 1000 ng/mL	-0.7–1.7% @ 1000 ng/mL
AM 9 (M1) 9-γ-hydroxyl	5–10	50–75	2.1% @ 1000 ng/mL	15% @ 1000 ng/mL	20.0% @ 1000 ng/mL	13% @ 667 ng/mL	7.3% @ 670 ng/mL 5.5% @ 1000 ngmL	-3.8–1.9% @ 1000 ng/mL
AM 4N (M21) 4-N-demethyl	3–5	5–25	6.0% @ 1000 ng/mL	<5% @ 1000 ng/mL	16.0% @ 1000 ng/mL	5.1% @ 500 ng/mL	<0.3% @ 500 ng/mL 0.9% @ 1000 ng/mL	-2.3–3.1% @ 1000 ng/mL
Abbreviations: ACMIA, affinity column-mediated immunoassay; CEDIA, cloned-enzyme donor immunoassay; EMIT, enzyme-multiplied immunoassay; and MEIA, microparticle enzyme immunoassay.

Table 2 Cross Reactivity of Sirolimus Major Metabolites
Metabolite	Bioactivity % 7, 8	Concentration Relative to Parent %	Seimens ACMIA	Syva EMIT	Abbott MEIA
39-O-demethyl (41-O-demethyl)	10	7	52% @ 0 ng/mL 60% @ 12 ng/mL	38% @ 0 ng/mL 42% @ 10 ng/mL	20.3% @ 10 ng/mL
16-O-demethyl (7-O-demethyl)	NS	4	10% @ 0 ng/mL 6% @ 12 ng/mL	15% @ 0 ng/mL 21% @ 10 ng/mL	7.6% @ 3 ng/mL
12 hydroxyl (11 hydroxyl)	7	11	46% @ 0 ng/mL 53% @ 12 ng/mL	4% @ 0 ng/mL 6% @ 10 ng/mL	36.8% @ 10 ng/mL
27, 39-O-didemethyl (41, 32-O-didemethyl)	NS	31	89% @ 0 ng/mL 83% @ 12 ng/mL	52% @ 0 ng/mL 61% @ 10 ng/mL	NS
Abbreviations: NS, not stated; ACMIA, affinity column-mediated immunoassay; EMIT, enzyme-multiplied immunoassay; and MEIA, microparticle enzyme immunoassay.

Table 3 Cross Reactivity of Tacrolimus Major Metabolites
Metabolite	Bioactivity % 5, 6	Concentration Relative to Parent %	Seimens ACMIA	Microgenics CEDIA	Syva EMIT	Abbott MEIA
M I 13-O-demethyl	6	6	14.8% @ 50 ng/mL	37.7% @ 20 ng/mL	10.4% @ 100 ng/mL	8% @ 10 ng/mL
M II 31-O-demethyl	100	15	2.7% @ 50 ng/mL	<AS @ 20 ng/mL	1.6% @ 100 ng/mL	94% @ 10 ng/mL
M III 15-O-demethyl	0	6	1.0% @ 50 ng/mL	<AS @ 20 ng/mL	2.2% @ 100 ng/mL	45% @ 10 ng/mL
M IV 12 hydroxyl	3.5	NS	18.0% @ 50 ng/mL	NS	21.1% @ 100 ng/mL	9% @ 10 ng/mL
M V 15, 31-O-didemethyl	0	NS	0.5% @ 50 ng/mL	NS	2.5% @ 100 ng/mL	NS
Abbreviations: AS, analytical sensitivity; NS, not stated; ACMIA, affinity column-mediated immunoassay; CEDIA, cloned-enzyme donor immunoassay; EMIT, enzyme-multiplied immunoassay; and MEIA, microparticle enzyme immunoassay

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