NEOBASE NON-DERIVATIZED MSMS KIT, MODEL 3040
Device Facts
| Record ID | K083130 |
|---|---|
| Device Name | NEOBASE NON-DERIVATIZED MSMS KIT, MODEL 3040 |
| Applicant | Perkinelmer, Inc. |
| Product Code | NQL · Clinical Chemistry |
| Decision Date | Jul 9, 2009 |
| Decision | SESE |
| Submission Type | Traditional |
| Regulation | 21 CFR 862.1055 |
| Device Class | Class 2 |
| Attributes | Pediatric |
Intended Use
The NeoBase Non-derivatized MSMS reagent kit is intended for the measurement and evaluation of amino acids, succinylacetone, free carnitine, and acylcarnitine concentrations from newborn heel prick blood samples dried on filter paper. Quantitative analysis of these analytes (Table 1) and their relationship with each other is intended to provide analyte concentration profiles that may aid in screening newborns for metabolic disorders.
Device Story
NeoBase Non-derivatized MSMS Kit measures amino acids, succinylacetone, free carnitine, and acylcarnitines in newborn dried blood spots. Extraction of blood spots occurs using a solution containing stable-isotope labeled internal standards. Analysis utilizes tandem mass spectrometry (MSMS) to determine analyte concentrations by comparing signal intensities of analytes to internal standards. Used in clinical laboratories; operated by trained technicians. Output provides analyte concentration profiles; aids healthcare providers in screening newborns for metabolic disorders. Non-derivatized format eliminates sample conversion to butyl esters, simplifying workflow compared to derivatized methods. Benefits include improved detection of Tyrosinemia Type I via succinylacetone measurement.
Clinical Evidence
Clinical correlation study at two US newborn screening labs using 9,416 random neonatal samples, 104 true positives, and 320 enriched dried blood spots. Compared NeoBase to predicate. Concordance assessed by agreement on analyte concentrations relative to cutoffs; agreement rates ranged from 97.2% to 100%. NeoBase demonstrated equivalent sensitivity to predicate for most disorders and superior detection for Tyrosinemia Type I due to SA measurement.
Technological Characteristics
Microplate-based tandem mass spectrometry (MSMS) assay. Uses stable-isotope labeled internal standards. Analyte extraction via incubation with extraction solution (succinylacetone requires specific derivatization). Triple-quadrupole mass spectrometer (MS² or QMicro systems). Connectivity via system-integrated software. Sterilization not applicable (reagent kit).
Indications for Use
Indicated for newborn screening of metabolic disorders using dried blood spot samples. Not intended for confirmatory or prenatal testing.
Regulatory Classification
Identification
A newborn screening test system for amino acids, free carnitine, and acylcarnitines using tandem mass spectrometry is a device that consists of stable isotope internal standards, control materials, extraction solutions, flow solvents, instrumentation, software packages, and other reagents and materials. The device is intended for the measurement and evaluation of amino acids, free carnitine, and acylcarnitine concentrations from newborn whole blood filter paper samples. The quantitative analysis of amino acids, free carnitine, and acylcarnitines and their relationship with each other provides analyte concentration profiles that may aid in screening newborns for one or more inborn errors of amino acid, free carnitine, and acyl-carnitine metabolism.
Special Controls
*Classification.* Class II (special controls). The special control is FDA's guidance document entitled “Class II Special Controls Guidance Document: Newborn Screening Test Systems for Amino Acids, Free Carnitine, and Acylcarnitines Using Tandem Mass Spectrometry.” See § 862.1(d) for the availability of this guidance document.
Predicate Devices
- NeoGram Amino Acids and Acylcarnitines Tandem Mass Spectrometry Kit (k031878)
Related Devices
- K093916 — NEOBASE NON-DERIVATIZED MSMS KIT MODEL 3040-001U · Perkinelmer, Inc. · Aug 23, 2010
- K173568 — NeoBase 2 Non-derivatized MSMS Kit · Wallac Oy, Subsidiary of Perkinelmer, Inc. · Sep 4, 2018
- K193103 — NeoBase 2 Non-derivatized MSMS Kit · Perkinelmer, Inc. · Feb 7, 2020
Submission Summary (Full Text)
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### 510(k) SUMMARY
This summary of 510(k) safety and effectiveness information is supplied in accordance with the requirements of the SMDA of 1990 and 21 CFR 807.92
The assigned 510(k) number is K083130.
Date: July 6, 2009
Submitted by:
Wallac Oy - PerkinElmer Inc. Mustionkatu 6 20750 Turku, Finland
Contact person:
Primary:
Kay A. Taylor Tele: 317-418-1735 Fax: 317-536-3064
Secondary:
Raija Koskivaara Tele: +358-2-2678 111 Fax: +358-2-2678 357
Trade Name:
NeoBase Non-derivatized MSMS Kit
Common Name: NeoBase kit or Non-derivatized kit
Classification Name: Newborn screening test system for amino acids, free carnitine, and acylcarnitines using tandem mass spectrometry (21 CFR § 862.1055 /Product code NQL)
NeoGram Amino Acids and Acylcarnitines Tandem Predicate device(s): Mass Spectrometry Kit, K031878
Device description: The measurement of amino acids, succinylacetone, free carnitine, and acylcarnitines with the NeoBase assay involves extraction of dried blood spots from newborns with a solution containing stable-isotope labeled internal standards and analysis using a tandem mass spectrometry (MSMS) system. The response of each analyte relative to their
{1}------------------------------------------------
corresponding stable-isotope labeled internal standard is proportional to analyte concentration
The NeoBase Non-derivatized MSMS reagent kit is Intended Use: intended for the measurement and evaluation of amino acids, succinylacetone, free carnitine, and acylcarnitine concentrations from newborn heel prick blood samples dried on filter paper. Quantitative analysis of these analytes (Tabel 1) and their relationship with each other is intended to provide analyte concentration profiles that may aid in screening newborns for metabolic disorders.
#### PerkinElmer MS2 Tandem Mass Spectrometer Instruments: . System and,
- PerkinElmer MS/MS Qmicro Screening System
| ANALYTE NAME | ABBREVIATION |
|--------------------------------------------------|----------------|
| Amino acids | |
| Alanine | Ala |
| Arginine | Arg |
| Citrulline | Cit |
| Glycine | Gly |
| Leucine/Isoleucine/Hydroxyproline* | Leu/lle/Pro-OH |
| Methionine | Met |
| Ornithine | Orn |
| Phenylalanine | Phe |
| Proline | Pro |
| Tyrosine | Tyr |
| Valine | Val |
| Carnitines | |
| Free carnitine | C0 |
| Acetylcarnitine | C2 |
| Propionylcarnitine | C3 |
| Malonylcarnitine / 3-Hydroxy-butyrylcarnitine* | C3DC/C4OH |
| Butyrylcarnitine | C4 |
| Methylmalonyl / 3-Hydroxy-isovalerylcarnitine* | C4DC/C5OH |
| Isovalerylcarnitine | C5 |
| Tiglylcarnitine | C5:1 |
| Glutarylcarnitine / 3-Hydroxy-hexanoylcarnitine* | C5DC/C6OH |
| Hexanoylcarnitine | C6 |
| Adipylcarnitine | C6DC |
| Octanoylcarnitine | C8 |
| Octenoylcarnitine | C8:1 |
- Alan de civation d MCMC Kit . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
{2}------------------------------------------------
| Decanoylcarnitine | C10 |
|----------------------------------------------|--------------|
| Decenoylcarnitine | C10:1 |
| Decadienoylcarnitine | C10:2 |
| Dodecanoylcarnitine | C12 |
| ANALYTE NAME | ABBREVIATION |
| Carnitines | |
| Dodecenoylcarnitine | C12:1 |
| Tetradecanoylcarnitine (Myristoylcarnitine) | C14 |
| Tetradecenoylcarnitine | C14:1 |
| Tetradecadienoylcarnitine | C14:2 |
| 3-Hydroxy-tetradecanoylcarnitine | C14OH |
| Hexadecanoylcarnitine (palmitoylcarnitine) | C16 |
| Hexadecenoylcarnitine | C16:1 |
| 3-Hydroxy-hexadecanoylcarnitine | C16OH |
| 3-Hydroxy-hexadecenoylcarnitine | C16:1OH |
| Octadecanoylcarnitine (Stearoylcarnitine) | C18 |
| Octadecenoylcarnitine (Oleylcarnitine) | C18:1 |
| Octadecadienoylcarnitine (Linoleylcarnitine) | C18:2 |
| 3-Hydroxy-octadecanoylcarnitine | C18OH |
| 3-Hydroxy-octadecenoylcarnitine | C18:1OH |
| Ketones | |
| Succinylacetone | SA |
*Analytes in these rows are either isomers or isobars and cannot be distinguished in the tandem mass spectrometry experiment.
# Device Comparison:
Table 5.1: Comparison of the NeoBase Non-derivatized MSMS and predicate device.
.
| GENERAL CHARACTERISTICS | | |
|-------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Parameter | NeoBase Non-derivatized MSMS kit | Predicate Device |
| Intended Use | The NeoBase Non-derivatized MSMS<br>reagent kit is intended for the<br>measurement and evaluation of amino<br>acids, succinylacetone, free carnitine,<br>and acylcarnitine concentrations from<br>newborn heel prick blood samples dried<br>on filter paper. Quantitative analysis of<br>these analytes (Table 1) and their<br>relationship with each other is intended<br>to provide analyte concentration profiles<br>that may aid in screening newborns for<br>metabolic disorders.<br>[intended use employs a table to<br>identify each analyte detected] | The NeoGram Amino Acids and<br>Acylcarnitines Tandem Mass<br>Spectrometry kit is intended for the<br>measurement and evaluation of<br>amino acids, free carnitine, and<br>acylcarnitine concentrations from<br>newborn heel prick blood samples<br>dried on filter paper. Table 1 details<br>the analytes measured by the kit<br>Quantitative analysis of amino<br>acids, free carnitine, and<br>acylcarnitine and their relationship<br>with each other is intended to<br>provide analyte concentration<br>profiles that may aid in screening<br>newborns for one or more of<br>several metabolic disorders. This<br>kit is to be used for in vitro |
{3}------------------------------------------------
| Disorders Screened | Amino-, organic-, and fatty acid<br>metabolic disorders | Same |
|---------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------|
| Analytes Measured | Amino acids, free carnitine,<br>acylcarnitines, and succinylacetone | Amino acids, free carnitine, and<br>acylcarnitines |
| Methodology | Microplate based tandem mass<br>spectrometric assay | Same |
| Test Principle | Amino acids and carnitines in sample<br>are measured by tandem mass<br>spectrometry through analyte-specific<br>mass transitions appropriate for each<br>type of analyte. The extracted analytes<br>are measured for set time periods and<br>compared to the signal intensities<br>produced by the corresponding isotope-<br>labeled internal standards. The<br>concentrations are determined by<br>comparing the signal intensities of the<br>known standards to the measured<br>analytes. | Same |
| Quantitative Nature | Quantitative by internal standardization | Same |
| Sample Requirements | Newborn blood collected on Schleicher<br>and Schuell 903 filter paper per NCCLS<br>standards | Same |
| Throughput | Ninety-six tests per microtiter plate.<br>Multiple plates can be analyzed | Same |
| Analysis Time | 2 to 2.5 hours per plate. | Same |
| Controls | Controls are blood spots from<br>processed human blood enriched with<br>several amino acids, carnitines and<br>succinylacetone. | Controls are blood spots from<br>processed human blood enriched<br>with several amino acids and<br>carnitines. |
| Calibrators | Internal calibration using several<br>isotopically labeled standards, included<br>as dried material in vials. Internal<br>standards must be reconstituted with<br>extraction solution prior to their use. | Same |
| Assay format | Non-derivatized (analytes measured in<br>their native forms) | Derivatized (analytes converted to<br>butyl esters prior to being<br>measured) |
11 - 1 - 1 - 1
# Analytes measured by the device
:
.
:
| Table 5.2: Analytes measured by the NeoBase kit and their most common abbreviated names | |
|-----------------------------------------------------------------------------------------|--------------|
| ANALYTE NAME | ABBREVIATION |
| Amino acids | |
| Alanine | Ala |
| Arginine | Arg |
| Citrulline | Cit |
| Glycine | Gly |
:
1
·
{4}------------------------------------------------
| Leucine/Isoleucine/Hydroxyproline* | Leu/Ile/Pro-OH |
|-----------------------------------------------------------------------------------------------------|----------------|
| Methionine | Met |
| Ornithine | Orn |
| Phenylalanine | Phe |
| Proline | Pro |
| Tyrosine | Tyr |
| Valine | Val |
| Carnitines | |
| Free carnitine | C0 |
| Acetylcarnitine | C2 |
| Propionylcarnitine | C3 |
| Malonylcarnitine / 3-Hydroxy-butyrylcarnitine* | C3DC/C4OH |
| Butyrylcarnitine | C4 |
| Methylmalonyl / 3-Hydroxy-isovalerylcarnitine* | C4DC/C5OH |
| Isovalerylcarnitine | C5 |
| Tiglylcarnitine | C5:1 |
| Glutarylcarnitine / 3-Hydroxy-hexanoylcarnitine* | C5DC/C6OH |
| Hexanoylcarnitine | C6 |
| Adipylcarnitine | C6DC |
| Octanoylcarnitine | C8 |
| Octenoylcarnitine | C8:1 |
| Decanoylcarnitine | C10 |
| Decenoylcarnitine | C10:1 |
| Decadienoylcarnitine | C10:2 |
| Dodecanoylcarnitine | C12 |
| Dodecenoylcarnitine | C12:1 |
| Table 5.2: Analytes measured by the NeoBase kit and their most common abbreviated names (continued) | |
| Tetradecanoylcarnitine (Myristoylcarnitine) | C14 |
| Tetradecenoylcarnitine | C14:1 |
| Tetradecadienoylcarnitine | C14:2 |
| 3-Hydroxy-tetradecanoylcarnitine | C14OH |
| Hexadecanoylcarnitine (palmitoylcarnitine) | C16 |
| Hexadecenoylcarnitine | C16:1 |
| 3-Hydroxy-hexadecanoylcarnitine | C16OH |
| 3-Hydroxy-hexadecenoylcarnitine | C16:1OH |
| Octadecanoylcarnitine (Stearoylcarnitine) | C18 |
| Octadecenoylcarnitine (Oleylcarnitine) | C18:1 |
| Octadecadienoylcarnitine (Linoleylcarnitine) | C18:2 |
| 3-Hydroxy-octadecanoylcarnitine | C18OH |
| 3-Hydroxy-octadecenoylcarnitine | C18:1OH |
| Ketones | |
| Succinylacetone | SA or SUAC |
*Analytes in these rows are either isomers or isobars and cannot be distinguished in the tandem mass spectrometry experiment.
# Substantial equivalency:
## (1) Non-clinical
The NeoBase Non-derivatized MSMS kit was compared to the predicate NeoGram Amino Acids and Acylcarnitines Tandem Mass Spectrometry Kit, k031878. Both devices utilize tandem mass spectrometry to measure a panel of
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amino acids and acvicarnitines from neonatal dried blood spots. The panel of analytes measured by both devices is the same with the main exception that the NeoBase kit also includes the measurement of succinylacetone (the primary marker for the screening of Tyrosinemia Type I). Analytically, both devices are also very similar with the exception that the NeoBase kit does not require the derivatization of the sample prior to measurement (Tables 5.1 and 5.2).
The established performance characteristics of the NeoBase kit were compared against the corresponding characteristics reported in the predicate device product insert. A summary of the performance characteristics is presented in Tables 5.3 to 5.6. Both kits provide equivalent precision and recoveries and both devices have measurable ranges that cover all clinically significant ranges. Therefore, both kits provide performance levels that are adequate for their intended use.
### Precision
Table 5.3: Averaged Total imprecision for amino acids. Data shown are average Total imprecision coefficients of variation (%CV) for both assays.
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Table 5.4: Averaged Total Imprecision for carnitine and acylcarnitines. Data shown are average Total imprecision coefficients of variation (%CV) for both assays.
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#### Recovery
#### Table 5.5: Averaged analyte percent recovery for both assays and associated %CV
| Analyte | NeoBase Recovery | | Predicate Recovery | |
|---------|------------------|-----|--------------------|-----|
| | Average % | %CV | Average % | %CV |
| ALA | 101 | 8 | 71 | 11 |
| ARG | 94 | 7 | 91 | 12 |
| CIT | 101 | 7 | 93 | 9 |
| GLY | 100 | 9 | 87 | 11 |
| LEU | 97 | 9 | 69 | 9 |
| MET | 89 | 6 | 89 | 18 |
| ORN | 91 | 7 | 72 | 14 |
| PHE | 99 | 7 | 96 | 22 |
| TYR | 101 | 6 | 81 | 11 |
| VAL | 90 | 10 | 68 | 16 |
| C0 | 93 | 7 | 139 | 12 |
{6}------------------------------------------------
| C2 | 97 | 6 | 67 | 23 |
|------|-----|---|-----|----|
| C3 | 100 | 5 | 97 | 19 |
| C4 | 94 | 4 | 104 | 11 |
| C5 | 98 | 6 | 111 | 7 |
| C5DC | 102 | 4 | 102 | 14 |
| C6 | 95 | 4 | 89 | 10 |
| C8 | 97 | 5 | 105 | 21 |
| C10 | 101 | 5 | 83 | 10 |
| C12 | 97 | 5 | 106 | 33 |
| C14 | 95 | 5 | 95 | 18 |
| C16 | 93 | 5 | 98 | 15 |
| C18 | 94 | 6 | 89 | 18 |
# Measurable Ranges
Table 5.6: Measurable ranges for both assays and corresponding clinically significant ranges (all in μM/L). and the comments of the comments of the comments of the comments of ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
| | NeoBase Range | | Predicate Range | | Clinical Ranges | |
|---------|---------------|-------|-----------------|--------|-----------------|------------|
| Analyte | Lower | Upper | Lower | Upper | Normal | Cutoff |
| ALA | 4.5 | 4109 | 4.92 | 2868.0 | 67 - 492 | 975 - 1625 |
| ARG | 0.6 | 3754 | 0.31 | 5469.0 | 0 - 58 | 180 - 300 |
| CIT | 4.8 | 1711 | 0.53 | 2169.2 | 0 - 36 | 113 - 188 |
| GLY | 50.4 | 4794 | 9.81 | 4023.3 | 238 - 808 | 975 - 1625 |
| LEU | 1.3 | 2598 | 9.06 | 3078.0 | 26 - 239 | 263 - 438 |
Table 5.6: Measurable ranges for both assays and corresponding clinically significant ranges (all in μM/L). Continued.
| Analyte | NeoBase Range | | Predicate Range | | Clinical Ranges | |
|---------|---------------|--------|-----------------|--------|-----------------|---------------|
| | Lower | Upper | Lower | Upper | Normal | Cutoff |
| MET | 2.5 | 1192 | 8.03 | 1476.7 | 3 - 59 | 120 - 200 |
| ORN | 0.6 | 3825 | 1.60 | 4675.4 | 5 - 214 | 360 - 600 |
| PHE | 0.3 | 2395 | 0.75 | 2906.0 | 10 - 130 | 225 - 375 |
| TYR | 1.2 | 2867 | 1.42 | 2537.1 | 14 - 194 | 578 - 963 |
| VAL | 0.6 | 2388 | 114.80 | 2900.0 | 34 - 213 | 300 - 500 |
| C0 | 0.2 | 2298 | 2.13 | 4143.0 | 6.6 - 70.6 | 90 - 150 |
| C2 | 0.2 | 732 | 0.13 | 166.3 | 6.2 - 44.3 | 128 - 213 |
| C3 | 0.03 | 88 | 0.09 | 130.7 | 0 - 4.9 | 9.75 - 16.25 |
| C4 | 0.07 | 59.61 | 0.02 | 58.4 | 0 - 0.92 | 2.25 - 3.75 |
| C5 | 0.04 | 58.73 | 0.02 | 101.6 | 0 - 0.61 | 1.88 - 3.13 |
| C5DC | 0.08 | 28.88 | 0.16 | 30.9 | 0 - 0.22 | 0.6 - 1 |
| C6 | 0.08 | 61.50 | 0.01 | 38.0 | 0 - 0.33 | 0.98 - 1.63 |
| C8 | 0.02 | 35.42 | 0.02 | 48.0 | 0 - 0.46 | 1.2 - 2 |
| C10 | 0.04 | 28.69 | 0.01 | 46.6 | 0 - 0.32 | 1.35 - 2.25 |
| C12 | 0.04 | 42.99 | 0.04 | 76.4 | 0 - 0.74 | 1.88 - 3.13 |
| C14 | 0.02 | 41.88 | 0.01 | 32.1 | 0 - 0.55 | 1.5 - 2.5 |
| C16 | 0.10 | 107.40 | 0.04 | 76.4 | 0.08 - 5.78 | 11.25 - 18.75 |
| C18 | 0.04 | 32.19 | 0.01 | 55.9 | 0.1 - 1.69 | 3 - 5.0 |
...
.
7
:
:
{7}------------------------------------------------
## Method Correlation
The method comparison study was executed based on the CLSI EP9-A2 quidelines. Samples were prepared in duplicates and assayed using both the NeoBase and NeoGram kits according to the corresponding kit inserts resulting in total of 158 samples acquired with each method. Each sample was tested twice within the same run within each method. Linear regression analysis provided correlation coefficients (R and R2) as well as slopes (Tables 5.7 to 5.9). The results from this study indicate that the test and predicate method correlated very well.
| Table 5.7: Method comparison: Correlation coefficient R and the Re for all amino acids. | | | | | |
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| Bell C. La branderson<br>SANNAGEMENTA<br>A March 1970 September 19<br>SANNARIA SA<br>CONTINUES ARANDISTRICAL A PARTICALL PA<br><br>FREE FREE FREE FREE STATUTE STATIS SALE STATUS ALL CONSULER A | A SECURE DE LES COLLECT SALES COLLECTION CONSULTATION COLLEGE ALL BE<br>The below to the country of the continued to the continued the continued the controlled<br>the first and the case the case be and the can be before of the before of | Concerner of the controllation of the commended of the commended of the commended of the commended of the commended of the commended of the commended of the commended of the<br>26 - 100 - 100 - 100 - 100 - 100 - 100 - 100 - 100 - 100 - 100 - 100 - 100 - 100 - 100 - 100 - 100 - 100 - 100 - 100 - 100 - 100 - 100 - 100 - 100 - 100 - 100 - 100 - 100 - 1<br>WWWW.<br>WWW<br>1111 NT a FA 1 0 1 0 1 0 1 0 1 0 1 0 1 0 1 0 1 0 1 0 1 0 1 0 1 0 1 0 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 | 86469698<br>NAMANA<br>4 . APAYAYAY LAYAS<br> | ATTACT<br>STATUTE OF COLUMN<br>SYATAYAS ===================================================================================================================================================================== | A PENSIONAL PAR<br>Conce of the ling that it in for a 11 45<br>A control and the designed the charges of the continues | <br>VAVAVA<br>------------------------------------------------------------------------------------------------------------------------------------------------------------------------------<br>****************************************************************************************************************************************************************************** | . But an and can be and can and any can be care and compares of<br>. I all and on the first of the first of the first of the first of the first of the first of the first of the first of the first of the first of the first of the first of the<br>464 68<br><br>AS (254762 | CONNECT COLLECTION CASIN A CALL PARTICLE PARTICLE LES PROFESSION PRODUCTION | SALEMAN<br> | |
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| 3000 142 4<br>. Conce as a class controllers and procession<br> | | | | | | | | | | |
| 1.0X 0X 03000 1 11 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1<br>resto Xest cases<br>WWWWAYAYAY<br>SAPARMICALA VA<br>URARA SERVER 16 A. A. A. A. S. A. | | | | | | | | | | |
Table 5.8: Method comparison: Correlation coefficient R and the R for free carnitine and acylcarnitines.
| ANTHAYAYAYAYAWAAWAYAYAYAYAYAYAYAYAYAY<br>WWW.VAVAVAYAYAYAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA<br>AMASHIPAYAYANINGAN = dPhyPANG PAYAYAYAYAY = AAMS<br>A be and can and a<br>.<br>Section and Controller and concession and the production and consideration and consideration and consideration and consideration and consideration and consideration and consi<br>the stop bet she labor and any of cancellantes for<br>VAVASMAAW<br>14444 6 6 4400<br>CONVAVA V | Act 40 - 100 -<br>. WANT | <br><br>All and all all all and the later of<br>Call of the Market M<br>A | WANDER AND A PARTIEN<br>. | | 1 . 1 . 0 . 0 . 0 . 0 . 0 . 0 . 0 . 0 . 0 . 0 . 0 . 0 . 0 . 0 . 0 . 0 . 0 . 0 . 0 . 0 . 0 . 0 . 0 . 0 . 0 . 0 . 0 . 0 . 0 . 0 . 0 . 0 . 0 . 0 . 0 . 0 . 0 . 0 . 0 . 0 . 0 . 0<br>STATUS STORE PASSES PARCOM PUSAN ASSOCIATION PRODUCTION PRODUCTION PRODUCTION PARTICLES PARTICLE PARTICLE PARTICLE PARTICLE PARTICLE PARTICLE PARTICLE PARTICLE PARTICLE PARTE<br>. | 10 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1<br>.<br> | <br>1 POWER PAYANA YA YA YA PARTHONOMICA WARA CA YA YA YA YA YA YA YA YA YA YA YA YA YA YA YA YA YA YA YA YA YA YA YA YA YA Y<br>Controller | CO COLOGO SUBCOLORIES COLOR PARMANIBULAN PHOTO CONSULAMANA PARA PARA PARA A PARA A PA | 16469<br>VALL STAS JATA<br>San Artist on Archite | |
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| contraction of the late of the lot also be and stores of<br>September of the Market of the State of the States of the States of the<br>MANAGAYAYAYAY<br>CHANAYAYAS<br>WANWAYAYAYAYA<br>IPAYAYAYAYAYA<br>PAPAYARAYAYAY<br>WAYAYAYAYAYAYA<br>AAPA/ASFAVAVAVAVA<br>AC STATA WAWA MAN<br>A A PARTA V A V A V A V A V A V A V A V A V A V A V A V A V A V A V A V A V A V A V A V A V A V A V A V A V A V A V A V A V A V A V A V A V A V A V A V A V A V A V A V A V A | | | | | | | | | | |
| . ALA CATAY AVAYA WASHA YA YA YA YA YA YA YA YA YA YA YA YA YA YA YA YA YA YA YA YA YA YA YA YA YA YA YA YA YA YA YA YA YA YA YA YA YA YA YA YA YA YA YA YA YA YA YA YA YA YA<br>AACQA@34AVA.COM AND WASCAYAYAYAYAY<br>������������������<br>400 V3.0 EVAVAT | on alleon from the considered to the considered to the | | | | | | | | | |
Table 5.9: Method comparison: Slopes and Intercepts for all amino acids.
| CON OF ANTIQUE ALL A LE A LE A LE A LE R LE R LE R LE R LE R LE B LE B LE B LE B LE B LE B LE B LE B LE B LE B LE B LE B LE B LE B LE B LE B LE B LE B LE B LE B LE B LE B LE<br>property and and on the see and and security of the second second second second server and server and the search and the send of the search of the seat to the season<br>のかんやるするとるやるやかなかなかなかったときとんどんなのかというかない<br>APAGATACAU.<br>S SARAARINIRIAAA SEUILLALA SEBUILUSARAARIUIRUARAAAA<br>Continued Concession of Concession Company of<br>Concession Collection Concession Concession Concessful Con-<br>Children Carder Carder Carder Carder Comparis Comments of Children Comments of Children Comments of Children Comments of Children Comments of Children Comments of Children Co<br>CHWWWWAYA<br>AMASSAT 6 P = PIN AHATAYAY AY 4<br>Max who well be to be a 2 a 3 | ANDARIA PRODUCTION CONSULTION CONSULTION CONSULTION CONSULTION CONSULTION CONSULTION CONSULTION CONSULTION CONSULTION CONSULTION CONSULTION CONSULTION CONSULTION CONSULTION C<br>CONSUMPINGBARAAA<br>STANNARAHIA<br>PAN A A B A P P A V A P M A P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P | A S A S A P A P A S P A P A P A P A V A V A V A V A V A V A V A V A V A V A V A V A V A V A V A V A V A V A V A V A | | <br>CARD CAR BALL MILL CLE CLASS CLASS AND AND AND | <br>ARAAL SALABAL A MANIS CAPA MANIGARAAN | STATUS COLLECTION CONSULTION CONSULTION CONSULTION PLACE CARACT COLLECTION CONSULTION CONSULTION CONSULTION CONSULTION CONSULTION CONSULTION CONSULTION CONSULTION CONSULTION<br>PARASTATAYAYAYAYAYAMAHAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA<br>PANNA<br>Property of Children<br>- WANDS -<br>ANYWA | 9.105 VATUAL<br>WWW<br>ARARACA UN A VAL<br>A LARA - Arden<br>1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1<br>CLAWANI<br>STATE CONTRACT OF COLLECTION OF COLLECTION OF CLASS OF COLLECTION OF COLLECTION OF COLLECTION OF COLLECTION OF COLLECTION OF COLLECTION OF COLLECTION OF COLLECTION OF COLLECT<br>PASSES SAN PARTICILITY<br>AMAYA VANDER WANDHIP<br><br>SHAWA | .<br>Carreland Controller<br>MARAMA<br>VWWW<br> | |
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| | | Court of the career and the can company and a minimally | Children Lead Children | | | | | | |
| ----------------------------------------------------------------------------------------------------------------<br>STANDES PARACE PARACO PARAL PARTIC LEA<br>PARTAPAYAYAPAYAWAHIPA APP PASS - VAPA<br><br>CORD AT LOUIS OF A ST SUBURBARA ARA<br>CONA and AVAY as Pour Con Pols un' car de<br>«РАУ«РАС : 189» | | | | | | | | | |
#### Table 5.10: Method comparison: Slopes and Intercepts for free carnitine and acvicarnitines.
| CALIFORNIA COLORIES LE LE COLORIES CONSULACIO C LECCRECARI CARAL PURCLES POLECTION CONSULTION CONSULTION CONSULTION CONSULTION CONSULTION CONSULTION CONSULTION CONSULTION CON<br>YAYAYAYAYAYAYAYAYAYAYAYAYAYAYAYAYAYAYAYAYAYAYAYAYAYAYAYAYAYAYAYAYAYAYAYAYA<br>Comments of the management of the many of the many and the many of the many of the first of the first of the first of the first<br>PARATES AND STATES PARTICAL . STACA ATATATA AND<br>93 WAVE SALV #BAY AMAR<br>.<br>.<br>14 10 10 1<br>PAYAYA AVA 969 PATATA<br>Cara Cara Cara Cara Cara Cara Cara Cara Cara Cara Cara Cara Cara Cara Cara Cara Cara Cara Cara Cara Cara Cara Cara Cara Cara Cara Cara Cara Cara Cara Cara Cara Cara Cara Cara<br>------------------------------------------------------------------------------------------------------------------------------------------------------------------------------<br> | 1 1 1 2000 AN COLORIAL I N AN AND SERVICE<br>WARMANNE<br>SEA STANKA SPA & SUPERAT SUPERATE PA<br>In any contracts and a<br>to the first of the late the first of a lot any and the first and the many of<br>AMANA MANHOWA<br>Canada Cara Canada | SING PAYAYAYAYAYAY<br>Callery of Children Company of Children Comments of Children Comments of Children Comments of Children Comments of Children Comments of Children Comments of Children Comments<br>****************************************************************************************************************************************************************************** | product any for aller. The first and alle | ****************************************************************************************************************************************************************************** | | PATION Co is Chan (an a can the first (first ) | 1 1 4 8 4 6 7 6 7 8 6 7 6 6 7 8 7 8 7 8 7 8 7 4 7 4 7 4 7 4 7 4 7 4 7 4 7 4 7 4 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 | <br>A CATAY CATATATA CONTROL CONSULTION CONSULTION CONSULTION CONSULTION CONSULTION CONSULTION CONSULTION CONSULTION CONSULTION CONSULTION CONSULTION CONSULTION CONSULTION CONSUL<br>19 2 2 2 4 2 4 2 4 2 4 2 6 9 4 2 6 2 4 7 6 2 6 2 6 2 6 2 6 2 6 2 6 2 6 2 6 6 2 6 6 2 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 | |
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| --------------------------------<br><br>Controller College of the |…
