Combining L2-records configuration with M3 method

Dear NMusers, Currently, I'm working on a project in which ceftriaxone measurements have been done for the free fraction and the total concentration. As both have been measured (almost) simultaneously, we've specified these as L2 records in our dataset. However, in a few records it occurs that one of the measurements (within one L2 record) may be below the LLOQ. Therefore, we've also included the M3 method to manage such measurements optimally.[1] Unfortunately, NONMEM is giving the following error: 0PROGRAM TERMINATED BY OBJ2 WITH INDIVIDUAL 2 ID= 2.00000000000000E+00 NONZERO VALUE OF F_FLAG CAN NOT BE USED WITHIN A MULTIPLE OBSERVATION L2 RECORD It seems that you cannot specify a F_FLAG of 1 within one of the L2 records. Therefore, the M3 method cannot be applied simultaneously with L2 records in your dataset. Although I can understand why this error occurs, I would like to know if there is a way to include both methods. We try to solve for the autocorrelation that may exist between the free (unbound) and the total concentration of ceftriaxone. Looking forward to receiving any answers/comments! Kind regards, *Dr. T. Preijers PharmD, PhD * *Hospital Pharmacist and Clinical Pharmacologist * Hospital Pharmacy Erasmus MC Rotterdam [1] Ahn JE, Karlsson MO, Dunne A, Ludden TM. Likelihood based approaches to handling data below the quantification limit using NONMEM VI. J Pharmacokinet Pharmacodyn. 2008 Aug;35(4):401-21.