SECTION 301 Pesticide Analytical Manual Vol I 301 B: CAPABILITIES AND LIMITATIONS OF MRMS Several aspects of an MRM influence its scope as a multiclass method:(1)thor- oughness with which the extraction solvent and physical procedure are capable of extracting residues from the sample, (2)ability of subsequent cleanup techniques to remove sample co-extractives without removing residues, and() the number of different determinative steps used to examine the extract During method devel- opment, a researcher evaluates each step of a method and makes choices based on optimum performance. Subsequent interlaboratory validation verifies that the method produces accurate results when performed as written This edition of PAM I presents MRMs as a series of modules, in recognition of standard practices in laboratories required to analyze many different commodities for many different potential residues Modules presented within the same section in this manual were not necessarily developed at the same time or by the same researcher Module combinations that have undergone interlaboratory validation are listed and recommended, but analysts may find it necessary to combine other modules to meet a particular need. Any such combination must be supported by with one another for the whole method to be applied in a valid manner mpatible data that validate its use in the situation. Steps of an MRM must be ce This section provides background information to assist the analyst in making valid choices and avoiding potential pitfalls. Included here are discussions about the overall influence solvents have on method performance and important informa tion about each category of method modules(extraction, cleanup, and determina- tive steps). Analysts combining method modules must be aware of the following concerns and take precautions to ensure that only appropriate combinations are Influence of solvents on Methodology Choice of solvent(s) is among the most important decisions made by a researcher of the following considerations related to solvents used in individual modules. re developing an analytical method. Analysts using these methods must also be aw Availability of Pure Solvent. Solvent purity is essential to avoid potential interfer ences in the determinative step; impurities are usually concentrated during the evaporation steps included in most residue methods. Higher purity solvents invari- ably cost more, and it may be possible to use less expensive, lower purity materials 204) supports their acceptability ed by appropriate determinative step(s)(Section if a solvent reagent blank exa Detector Response to Solvent. GlC detectors used in residue determinations are sually selective for an element in the analyte molecule, so the final extract must not be dissolved in a solvent containing element(s) to which the detector(s)re- spond. For example, no trace of acetonitrile can be present when a nitrogen- selective detector is used, and no methylene chloride when a halogen-selective detector is used. HPLC detectors commonly used in residue determination pre- clude use of solvents that absorb UV light or fluoresce at the wavelength used during determination Solvents can adversely affect detectors in other ways, such as the deleterious but poorly defined effect acetonitrile has on electroconductivity detectors Transmittal No 94-1(1/94) Form FDA 2905a(6/92301–4 Transmittal No. 94-1 (1/94) Form FDA 2905a (6/92) SECTION 301 Pesticide Analytical Manual Vol. I 301 B: CAPABILITIES AND LIMITATIONS OF MRMS Several aspects of an MRM influence its scope as a multiclass method: (1) thor￾oughness with which the extraction solvent and physical procedure are capable of extracting residues from the sample, (2) ability of subsequent cleanup techniques to remove sample co-extractives without removing residues, and (3) the number of different determinative steps used to examine the extract. During method devel￾opment, a researcher evaluates each step of a method and makes choices based on optimum performance. Subsequent interlaboratory validation verifies that the method produces accurate results when performed as written. This edition of PAM I presents MRMs as a series of modules, in recognition of standard practices in laboratories required to analyze many different commodities for many different potential residues. Modules presented within the same section in this manual were not necessarily developed at the same time or by the same researcher. Module combinations that have undergone interlaboratory validation are listed and recommended, but analysts may find it necessary to combine other modules to meet a particular need. Any such combination must be supported by data that validate its use in the situation. Steps of an MRM must be compatible with one another for the whole method to be applied in a valid manner. This section provides background information to assist the analyst in making valid choices and avoiding potential pitfalls. Included here are discussions about the overall influence solvents have on method performance and important informa￾tion about each category of method modules (extraction, cleanup, and determina￾tive steps). Analysts combining method modules must be aware of the following concerns and take precautions to ensure that only appropriate combinations are used. Influence of Solvents on Methodology Choice of solvent(s) is among the most important decisions made by a researcher developing an analytical method. Analysts using these methods must also be aware of the following considerations related to solvents used in individual modules: Availability of Pure Solvent. Solvent purity is essential to avoid potential interfer￾ences in the determinative step; impurities are usually concentrated during the evaporation steps included in most residue methods. Higher purity solvents invari￾ably cost more, and it may be possible to use less expensive, lower purity materials if a solvent reagent blank examined by appropriate determinative step(s) (Section 204) supports their acceptability. Detector Response to Solvent. GLC detectors used in residue determinations are usually selective for an element in the analyte molecule, so the final extract must not be dissolved in a solvent containing element(s) to which the detector(s) re￾spond. For example, no trace of acetonitrile can be present when a nitrogen￾selective detector is used, and no methylene chloride when a halogen-selective detector is used. HPLC detectors commonly used in residue determination pre￾clude use of solvents that absorb UV light or fluoresce at the wavelength used during determination. Solvents can adversely affect detectors in other ways, such as the deleterious but poorly defined effect acetonitrile has on electroconductivity detectors