{ "status": "Source-data unavailability qualified; authorized pivot to primary analytical specificity and PK intake", "inputs_sha256_lf_text": "0a22838bfeac0f27d19b0c0ce6715f532ad74816f17f02d0ab1e6062242eea0e", "hash_convention": "UTF-8 text after universal-newline normalization to LF", "MSC_units": { "human_donors": 12, "recipient_mice": 36, "combined_independent_sample_size": null, "histology_field_n_can_replace_mouse_n": false, "donor_linkage": { "numerical_donor_linked_metabolism_repair_reanalysis_eligible": false, "missing": [ "numeric_metabolic_values", "numeric_repair_values", "stable_individual_donor_ids", "culture_to_donor_crosswalk", "recipient_to_donor_crosswalk", "endpoint_unit_hierarchy_resolved" ], "effect_or_correlation_estimate": null } }, "analytical_scale_comparison": { "reported_LLOD_ng_per_mL": 0.1, "reported_ELISA_signal_range_ng_per_mL": [ 45.9, 218.5 ], "reported_ELISA_signal_to_LLOD_scale_ratio_range": [ 458.99999999999994, 2185.0 ], "n_reference_subjects": 20, "individual_paired_concentrations_available": false, "true_intact_parent_concentrations": null, "assay_bias_or_cross_reactivity_estimate": null, "universal_ELISA_failure_inferred": false, "interpretation": "Reported immunoassay-signal/LCMS-detection-limit scale separation only; not a true concentration bound, specificity proof, calibration slope, or PK parameter." }, "steady_state_identity": { "expression": "C_ss = F * R / CL", "scope": "Simple linear steady-state parent mass balance; R is administered parent input rate, F its systemic fraction, C_ss its exogenous intact-parent increment with endogenous contribution resolved.", "half_life_expression": "t_half = ln(2) * V / CL", "half_life_scope": "One-compartment linear disposition (or appropriate terminal distribution volume); neither V nor terminal slope follows from one steady-state immunoreactive concentration.", "K14Q_reported_apparent_clearance_slowing_factor": 2.6, "variant_specific_plasma_calibration_preserved": true, "interpretation": "Variant-specific calibration corrects lower assay sensitivity and is real evidence. It does not resolve intact molecular species, every product's cross-reactivity, endogenous baseline, input F or a decay half-life. Knoop's different commercial assay does not universally invalidate it.", "new_native_clearance_or_half_life_estimate": null }, "pk_eligibility": [ { "case_id": "MSC_cell_pretreatment", "context": "cell_pretreatment", "reported_timepoint_count": 0, "finite_interval_parent_AUC_intake_eligible": false, "terminal_half_life_intake_eligible": false, "absolute_parent_clearance_from_AUC_intake_eligible": false, "absolute_oral_F_intake_eligible": false, "missing_for_AUC": [ "source_reports_parent_specific_detection", "source_reports_quantitative_matrix_assay_validation", "baseline_or_endogenous_component_resolved", "administered_systemic_route_known", "serial_concentration_time_data", "in_vivo_systemic_administration_context", "at_least_two_quantified_concentration_time_pairs" ], "missing_for_terminal_half_life": [ "source_reports_parent_specific_detection", "source_reports_quantitative_matrix_assay_validation", "baseline_or_endogenous_component_resolved", "administered_systemic_route_known", "serial_concentration_time_data", "in_vivo_systemic_administration_context", "at_least_two_quantified_concentration_time_pairs", "sufficient_terminal_phase_sampling" ], "missing_for_absolute_clearance_from_AUC": [ "source_reports_parent_specific_detection", "source_reports_quantitative_matrix_assay_validation", "baseline_or_endogenous_component_resolved", "administered_systemic_route_known", "serial_concentration_time_data", "in_vivo_systemic_administration_context", "at_least_two_quantified_concentration_time_pairs", "systemic_input_fraction_known", "administered_parent_amount_known", "complete_parent_AUC_or_qualified_extrapolation" ], "missing_for_oral_F": [ "source_reports_parent_specific_detection", "source_reports_quantitative_matrix_assay_validation", "baseline_or_endogenous_component_resolved", "administered_systemic_route_known", "serial_concentration_time_data", "in_vivo_systemic_administration_context", "at_least_two_quantified_concentration_time_pairs", "paired_oral_iv_parent_auc_available", "dose_normalization_known", "route_comparison_context_qualified", "both_routes_complete_parent_AUC_or_qualified_extrapolation" ], "numerical_AUC_half_life_clearance_or_F": null, "gate_limit": "Source-presence checks for concentration-time/AUC accounting only; the separate steady-state identity does not require a decay series. No data fit or quantitative inference is made by a passing gate." }, { "case_id": "Knoop_endogenous_reference", "context": "endogenous_observation", "reported_timepoint_count": 0, "finite_interval_parent_AUC_intake_eligible": false, "terminal_half_life_intake_eligible": false, "absolute_parent_clearance_from_AUC_intake_eligible": false, "absolute_oral_F_intake_eligible": false, "missing_for_AUC": [ "baseline_or_endogenous_component_resolved", "administered_systemic_route_known", "serial_concentration_time_data", "in_vivo_systemic_administration_context", "at_least_two_quantified_concentration_time_pairs" ], "missing_for_terminal_half_life": [ "baseline_or_endogenous_component_resolved", "administered_systemic_route_known", "serial_concentration_time_data", "in_vivo_systemic_administration_context", "at_least_two_quantified_concentration_time_pairs", "sufficient_terminal_phase_sampling" ], "missing_for_absolute_clearance_from_AUC": [ "baseline_or_endogenous_component_resolved", "administered_systemic_route_known", "serial_concentration_time_data", "in_vivo_systemic_administration_context", "at_least_two_quantified_concentration_time_pairs", "systemic_input_fraction_known", "administered_parent_amount_known", "complete_parent_AUC_or_qualified_extrapolation" ], "missing_for_oral_F": [ "baseline_or_endogenous_component_resolved", "administered_systemic_route_known", "serial_concentration_time_data", "in_vivo_systemic_administration_context", "at_least_two_quantified_concentration_time_pairs", "paired_oral_iv_parent_auc_available", "dose_normalization_known", "route_comparison_context_qualified", "both_routes_complete_parent_AUC_or_qualified_extrapolation" ], "numerical_AUC_half_life_clearance_or_F": null, "gate_limit": "Source-presence checks for concentration-time/AUC accounting only; the separate steady-state identity does not require a decay series. No data fit or quantitative inference is made by a passing gate." }, { "case_id": "Knoop_storage_caption", "context": "sample_storage", "reported_timepoint_count": 0, "finite_interval_parent_AUC_intake_eligible": false, "terminal_half_life_intake_eligible": false, "absolute_parent_clearance_from_AUC_intake_eligible": false, "absolute_oral_F_intake_eligible": false, "missing_for_AUC": [ "source_reports_parent_specific_detection", "source_reports_quantitative_matrix_assay_validation", "baseline_or_endogenous_component_resolved", "administered_systemic_route_known", "serial_concentration_time_data", "in_vivo_systemic_administration_context", "at_least_two_quantified_concentration_time_pairs" ], "missing_for_terminal_half_life": [ "source_reports_parent_specific_detection", "source_reports_quantitative_matrix_assay_validation", "baseline_or_endogenous_component_resolved", "administered_systemic_route_known", "serial_concentration_time_data", "in_vivo_systemic_administration_context", "at_least_two_quantified_concentration_time_pairs", "sufficient_terminal_phase_sampling" ], "missing_for_absolute_clearance_from_AUC": [ "source_reports_parent_specific_detection", "source_reports_quantitative_matrix_assay_validation", "baseline_or_endogenous_component_resolved", "administered_systemic_route_known", "serial_concentration_time_data", "in_vivo_systemic_administration_context", "at_least_two_quantified_concentration_time_pairs", "systemic_input_fraction_known", "administered_parent_amount_known", "complete_parent_AUC_or_qualified_extrapolation" ], "missing_for_oral_F": [ "source_reports_parent_specific_detection", "source_reports_quantitative_matrix_assay_validation", "baseline_or_endogenous_component_resolved", "administered_systemic_route_known", "serial_concentration_time_data", "in_vivo_systemic_administration_context", "at_least_two_quantified_concentration_time_pairs", "paired_oral_iv_parent_auc_available", "dose_normalization_known", "route_comparison_context_qualified", "both_routes_complete_parent_AUC_or_qualified_extrapolation" ], "numerical_AUC_half_life_clearance_or_F": null, "gate_limit": "Source-presence checks for concentration-time/AUC accounting only; the separate steady-state identity does not require a decay series. No data fit or quantitative inference is made by a passing gate." }, { "case_id": "K14Q_pump_ELISA", "context": "steady_state_extravascular_infusion", "reported_timepoint_count": 1, "finite_interval_parent_AUC_intake_eligible": false, "terminal_half_life_intake_eligible": false, "absolute_parent_clearance_from_AUC_intake_eligible": false, "absolute_oral_F_intake_eligible": false, "missing_for_AUC": [ "source_reports_parent_specific_detection", "source_reports_quantitative_matrix_assay_validation", "baseline_or_endogenous_component_resolved", "serial_concentration_time_data", "at_least_two_quantified_concentration_time_pairs" ], "missing_for_terminal_half_life": [ "source_reports_parent_specific_detection", "source_reports_quantitative_matrix_assay_validation", "baseline_or_endogenous_component_resolved", "serial_concentration_time_data", "at_least_two_quantified_concentration_time_pairs", "sufficient_terminal_phase_sampling" ], "missing_for_absolute_clearance_from_AUC": [ "source_reports_parent_specific_detection", "source_reports_quantitative_matrix_assay_validation", "baseline_or_endogenous_component_resolved", "serial_concentration_time_data", "at_least_two_quantified_concentration_time_pairs", "systemic_input_fraction_known", "administered_parent_amount_known", "complete_parent_AUC_or_qualified_extrapolation" ], "missing_for_oral_F": [ "source_reports_parent_specific_detection", "source_reports_quantitative_matrix_assay_validation", "baseline_or_endogenous_component_resolved", "serial_concentration_time_data", "at_least_two_quantified_concentration_time_pairs", "paired_oral_iv_parent_auc_available", "dose_normalization_known", "route_comparison_context_qualified", "both_routes_complete_parent_AUC_or_qualified_extrapolation" ], "numerical_AUC_half_life_clearance_or_F": null, "gate_limit": "Source-presence checks for concentration-time/AUC accounting only; the separate steady-state identity does not require a decay series. No data fit or quantitative inference is made by a passing gate." } ], "eligible_numerical_parent_pk_datasets": 0, "oral_F_assigned": null, "delivery_or_analogue_functional_rank": null, "source_observations_digitized_or_synthesized": false }