2018 August 26 SPSFAM Book

System suitability tests and/or analytical quality  control: • The performance criteria in Table 1 are  for single laboratory validation.  • Method developers contemplating a 

multi‐lab validation study should  contact AOAC for developing a  collaborative study design.    

Comments Submitted -

TypesofComments CommentorConcern (Justification forChange ‐IncludeLineNumber if  Applicable)

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Response

See above 

1) Maintain criterion aswritten. The goal is tohave a  sharp distintion between 0.5MRLand 1.0MRL with  a low rate of false positives.  2) No change. 90analyses  canbe from a cocktailof  drugs run simultaneously in a matrix, but cannotbe  pooled acrossmatrices. See footnotea.  3) Clarify text in Validation Guidance (Section 7)as "For  identification, method developers must provide the  precursor ion and at least twoSRM  transitions with  ion ratios".The intent was tohave themethod  developer provide transitions and justify their  methodology for identification.  4) Remove shading wherenumbers havebeen added.  5) Change as suggested. Delete Cetiofur asa regulated  marker.  6) Change as suggested. 7) Change as suggested. 8) Discussion needed ‐ EU specifies (2R,3S,4R,5R,8R,  10R,11R,12S,13S ,14R)‐2‐ethyl3,4,10,13‐ tetrahydroxy3,5,8,10,12,14‐hexamethyl‐11‐ [[3,4,6‐

Technical Editorial

1)Table1–PODcriteria for0.5MRL–Should the criteriabe “≥10%  POD”asopposed to “≤10%POD”at0.5MRL?  Itmakes sense that it is  lessorequal10% forblanks but itneeds tobeallowed tobeabove10%  for0.5MRL. 2)Table1–n=30 forblanks,0.5MRLandMRLmeans90 runs foreach  analyte‐matrix combination, which isavery largenumberofanalyses  just togetonedatapoint.  Couldpooled databeusedacrossmultiple  matrices? 3)Thereareno criteria for “identification”.  POD isused fordetection.   POI isused for identification.  I recommendeither changing “POD” to  “POD/POI” inTable1andaddingPOIdefinition to theDefinition part.   Alternatively, there shouldbeanote that theanalyteneeds tobeboth  detectedand identified.  Forexample for LC‐MS/MSmethods,an  analyte canbedetected usinga singleMS/MS transition, however, at  least2MS/MS transitions are required for identification purposes. 4)Table2–Thereare some cells thatare shaded but contain anumber.  This should beeitherexplained or corrected (shadingornumber  removedasapplicable).  Examples:  Acetylisovaleryltylosin in chicken  muscle (40ppb); cefuroxime inbovine muscleand fat (both20ppb);  enramycin in chicken fatandmuscle (bothat30ppb)and someothers 5)Ceftiofur –marker residue definition should be: “Sumofall residues  retaining thebeta‐lactam structure,expressed asdesfuroylceftuiofur” 6)Doxycycline –remove “doxycycline” in themarker column. 7)Change“morentel” to “morantel”and itsmarker residue definition  should be “Sumof residueswhichmaybehydrolyzed toN‐methyl‐1,3‐ propanediamine andexpressed asmorantelequivalents”, which is  different than “N‐methyl‐1,3‐propanediamine” 8)Tulathromycin ‐marker residues are (2R,3S,4R,5R,8R,  10R,11R,12S,13S ,14R)‐2‐ethyl3,4,10,13‐tetrahydroxy3,5,8,10,12,14‐ hexamethyl‐11‐[[3,4,6‐trideoxy3‐(dimethylamino)‐β‐D‐ xylohexopyranosyl]ox y]‐1‐oxa‐6‐azacyclopentadecan‐15‐one  expressed as tulathromycin equivalents 9)Triclabendazole –marker residuedefinition should be: “Sumof the  extractable residues thatmaybeoxidized toketotriclabendazole”

trideoxy3‐(dimethylamino)‐β‐D‐ xylohexopyranosyl]ox y]‐1‐oxa‐6‐

azacyclopentadecan‐15‐oneasmarker residue, but  Canadaand US specify CP‐60,300asmarker residue.  9) Change as suggested.