Guidelines for Writing an SOP for Mass Spectrometryba333.free.fr/khira/Guidelines for Writing an SOP for... · Web viewGuidelines for Writing an SOP for Mass Spectrometry prepared

www.lanzarotecaliente.com (press control & click here)

Guidelines for Writing an SOP for Mass Spectrometry

prepared by the Measurements & Standards Committee of the American Society for Mass Spectrometry 1 September 1997

INTRODUCTION

The purpose of this document is to provide guidance and suggestions for writing Standard Operating Procedures (SOPs) for mass spectrometer systems (MS.) The focus is on SOPs for MS instrumentation that generates data in support of FDA filings. Other regulatory agencies, such as the EPA, which may have different requirements, are not covered. An

http://www.lanzarotecaliente.com/




overview of SOP formats and typical language is discussed. Several examples from SOPs currently in place in laboratories in the community are included as appendices. These guidelines are intended to provide a framework for implementing rational and useable MS SOPs. The Society takes no position on the applicability of any specific suggestion in this document or the examples shown for a specific laboratory operation. In fact, it is the Society's view that a "boilerplate" or "fill-in-the-blank" SOP probably cannot be written. Each laboratory situation is unique. Each laboratory needs to assess its current practices and in consultation with its Quality Assurance Unit design SOPs that meet its particular needs. Collaboration with the QAU is valuable as it represents the company's positions on GLP issues and because it will likely be the first group to audit the laboratory. Furthermore, the QAU may have an SOP that describes how laboratory SOPs should be written. In most instances, SOPs should document a laboratory's current practices, not legislate new ones: "write what you do and do what you write."

MS SOPs are only one part of an SOP package for mass spectrometry laboratories generating data for registrational purposes. An entire suite of SOPs might include, but not be limited to, assay validation procedures, study sample analysis procedures, personnel training, sample tracking, archiving of data and change control.

The main Federal regulations pertaining to this topic are from CFR Part 58, "Good Laboratory Practices for Nonclinical Laboratory Studies", Section 58.63 (reproduced here in its entirety) (1,2):

§ 58.63 Maintenance and calibration of equipment

a. Equipment shall be adequately inspected, cleaned, and maintained. Equipment used for the generation, measurement, or assessment of data shall be adequately tested, calibrated and/or standardized.

b. The written standard operating procedures required under ' 58.81(b)(11) shall set forth in sufficient detail the methods, materials, and schedules to be used in the routine inspection, cleaning, maintenance, testing, calibration, and/or standardization of equipment, and shall specify, when appropriate, remedial action to be taken in the event of failure or malfunction of equipment. The written standard operating procedures shall designate the person responsible for the performance of each operation.

c. Written records shall be maintained of all inspection, maintenance, testing, calibrating and/or standardizing operations. These records, containing the date of the operation, shall describe whether the maintenance operations were routine and followed the written standard operating procedures. Written records shall be kept of nonroutine repairs performed on equipment as a result of failure and malfunction. Such records shall document the nature of the defect, how and when the defect was discovered, and any remedial action taken in response to the defect.

Note that the regulations in this part apply specifically to nonclincial studies used for Investigational New Drug (IND) registration. Therefore, animal drug safety evaluation studies are covered under these regulations, while clinical studies in humans are not. However, other regulations in Chapter 48, Bioresearch Monitoring Human Drugs, require instrument SOPs for bioavailability and bioequivalence studies (3.) Further, any work performed to support Good Manufacturing Practices, GMP, must also be covered by instrument SOPs. Many members of the ASMS community have taken the position that their laboratories will operate under these regulations and use SOPs at all times. Nonetheless, if a mass spectrometry laboratory never does any nonclinical GLP work for FDA filings, GMP or bioavailability/bioequivalence testing, then that laboratory is not obligated to have MS SOPs. But, if an instrument is used, even occasionally, for experiments that will support an FDA

filing, an SOP for that instrument should be developed and followed. See Boyd, et al. (4), for an excellent report on the 1994 ASMS GLP workshop which includes a discussion on "colloquial" vs. narrow interpretations of the term "GLP."

Note that neither the title nor the body of Section 58.63 includes the word "operation". The MS SOPs should not be operator's manuals. The SOPs are meant to ensure that a particular instrument is properly maintained and calibrated such that any data generated from it when operating can be considered reliable. However, a laboratory may find it useful or important to provide synoptic operations manuals or "Laboratory Operations Guides", that fall outside the purview of SOP inspection criteria but provide critical information to instrument operators.

There are at least two general approaches to writing an MS SOP. The first might be termed a "system-independent" document and the second a "system-specific document." In the first case, the SOPs are written in a way general enough to cover the requirements of the regulations while encompassing a wide variety of instrument models. Using this approach, the laboratory might think it best to have separate SOPs for quadrupole and magnetic sector instruments, while still not differentiating between specific models. The second approach is to have SOPs for specific instrument models, e.g., one for a Finnigan TSQ 7000 and another for a PE Sciex API 300. Again, the best approach for a particular laboratory can only be determined by that laboratory after review and consideration of its current practices and in consultation with its QAU, if appropriate.

It is also important to keep in mind that SOPs are "living documents." That is, they can and should be modified on a regular basis as practices and procedures change. Further, it is acceptable to deviate from current SOPs if valid scientific reasons exist for such a deviation and the change is noted and supported in the appropriate study files and notebooks. Such a deviation may be temporary for a particular problem or may represent an overall improvement that should be included in the next SOP revision.

SOP FORMAT

An SOP document should consist of a title/information page and document body which usually includes five topics or sections: Purpose, Scope, Introduction, Responsibilities and Procedures. The first four of these sections provide the ground rules for the SOP, what it encompasses, how it is to be applied, while the procedure section provides the details of what needs to be done. This is not the only way to write an SOP, but this format provides fairly clear delineation of the various aspects an SOP is expected to cover for the regulations. It certainly seems possible, for example, that the first four sections might be contained within a single section as an Introduction. In any event, the SOP should meet internal requirements on formatting, writing and changing SOPs.

Title/information page

In addition to the title, the title page contains a procedure number incorporating some form of version control, the author(s) name(s), approval name(s), signatures and dates of signatures for all, an effective date for the procedure and total number of pages in the document. A title might be "Maintenance and Calibration of Mass Spectrometer Systems" or "Maintenance and Calibration of a Sciex API III Mass Spectrometer." A procedure number could be "INST00006.01" where this is version 1 of the sixth in a series of instrument SOPs.

It's a good idea to include the author names as that provides a point of reference for those with questions about the intent of certain language and it also provides a logical "volunteer" for SOP re-evaluation and revision. Management sign-off indicates awareness of the document, approval of its contents and assurance of enforcement.

Finally, dates, especially effective dates, are very important for historical control. These show which SOP version was in force when a particular study was analyzed. It is important to keep copies of old SOPs that are no longer in force for an auditor's review in case an audit is directed at studies that were run under older versions of a particular SOP. Thus the study can be audited based on the procedures in place at the time, not on current, perhaps different procedures.

Purpose

This section simply describes the focus of the SOP, which, in this case, is to provide a maintenance and calibration procedure for the instrument(s) defined in the title.

Scope

This section defines the applicability of the SOP, i.e., the work that will be subject to be the provisions of the SOP. It could, for example, indicate whether only nonclinical GLP studies are subject to the terms of SOP or all data generated to support registrational filings or something in between.

Introduction

The SOP introduction provides background material for the procedure. A list of defined terms can be included in this section. This is good place to define the mass spectrometer - is it just the mass analyzer and supporting hardware, excluding data systems and inlet systems, or is an LC/MS, for example, an all-inclusive system consisting of the HPLC, the MS and the DS? The latter provides the advantage of the "black box" approach to instrument performance verification,

Responsibilities

This section defines the person(s) who is going to be responsible for ensuring that the procedure is implemented. This can be a single individual or it can be generic to state that the person running the instrument to generate data covered by this SOP is the responsible individual (RI).

Procedures

The procedures section will be the most detailed part of the SOP in which required procedures for "maintenance and calibration" of the mass spectrometer(s) are itemized and described. Before writing this section, it is very important to review and analyze current laboratory procedures. It is likely that most of the everyday practices currently in place in a particular laboratory are adequate, not only for good science, but also for the purposes of the SOP. Thus all that is required is to formalize them by writing them down as an SOP, including a procedure to document compliance. If deficiencies exist in maintenance and calibration procedures, this may be good time to fix them, but the "wouldn't it nice if we did this" syndrome should be avoided. Again "write what you do and do what you write." It is very important to remember that the procedures listed in the SOP will form the basis of evaluation for an audit. For example, if a procedure in the SOP specifies calibrating an instrument with PFTBA everyday before use, then, to be in compliance, not only must the calibration be performed daily (within the work scope of the SOP) but it must be documented in such a way that an auditor can verify that it was in fact done (e.g., dated, signed copy of the PFTBA spectrum, including a statement of acceptability.) If, in the best judgment of the laboratory, daily calibration of an instrument with PFTBA is unnecessary, then such a procedure should not be included in the SOP.

Maintenance items would include source cleaning and changing vacuum pump fluids, as well as general inspections, such as checking vacuum levels and temperature-controlled zones. Schedules for performing the maintenance items should be included in some form. For example, source cleaning could be tied to an instrument performance criterion rather than to the calendar. Formal preventive maintenance (PM), on the other hand, may be better put on a calendar basis, but the time frame should be flexible enough to allow for scheduling delays. For example, a PM might be specified for every 6-12 months or 12-18 months, as appropriate to the particular equipment.

Calibration would most obviously include mass axis calibration, but in some instances might include such things as voltage calibrations of power supplies, for example. Calibration procedures should also include some acceptance guidelines, e.g., "determined m/z of calibrant ion shall be within 0.1 amu of theoretical." Depending on the circumstance, standard reference compounds, such as PFTBA or PEGs might be the preferred calibrant or the analytes for a particular analysis might be a better choice. In either case, the calibrants should be well-characterized reference materials. A laboratory performing qualitative analysis or structural identification, would probably use standard reference materials. On the other hand, a laboratory in the quantitative analysis business might find use of the actual analytes as calibrants to be very useful. In either case, the SOP should be probably be written to allow making either choice, or some combination, depending on the circumstance and at the discretion of the scientist involved.

One approach used by some labs, is to have an SOP for general instrument maintenance and calibration procedures and rely on specific analytical methods for actual operation and sample analysis. Language in the SOP references analytical methods as the source for operating details for a given analysis. This works particularly well for quantitative analysis, where analytical methods include critical details on instrument parameters and special calibrations which might be required for a particular analyte. Such methods might include system suitability testing where the entire analytical system, chromatographic performance as well as the sensitivity and resolution of the mass spectrometer for the compounds of interest, would be examined prior to running a set of samples (a "black box" approach.) Thus, system suitability testing might obviate the need for more general calibrations that might otherwise be called for in an SOP.

Finally, the procedure should itemize how the specified practices will be documented. Some instrument parameters might be best documented in a spreadsheet on the instrument's computer. Service reports are probably most easily stored in a binder of some sort. The regulations require that any instrument malfunction be documented with the nature of the problem, who discovered it, and how it was corrected. Vendor service reports might suffice for this purpose, if they include, or can be made to include, all required information, such as the symptom of the problem, in sufficient detail. Further, system qualification after service should be documented.

SUMMARY

This document hopes to provide approaches and suggestions for promulgation of Standard Operating Procedures for mass spectrometers, which is only one of many SOPs required for a laboratory supplying registrational data. While the main focus of this writing is to provide guidelines for MS laboratories that need to be in regulatory compliance, the intent of SOPs should also be to promote good science and to try to ensure high quality experimental results. The regulations do not specify how to write SOPs or maintain and calibrate instruments; those decisions fall to the laboratories and should reflect the sound scientific and real-world practices of the individuals involved. The over-arching principle in generating

SOPs is always to document current practices, not legislate new ones. A corollary is that SOPs are living documents: as practices and procedures evolve, so must SOPs.

REFERENCES

1. Code of Federal Regulations, Title 21, Food and Drugs; Office of the Federal Register, National Archives and Records Administration: Washington, DC, 1994; Part 58. (Available from: New Orders, PO Box 371954, Pittsburgh, PA, 15250-7954.

2. FDA Compliance Program Guidance Manual. Chapter 48: Human Drugs Bioresearch Monitoring. Program 7348.808, Good Laboratory Practice (Nonclinical Laboratory.) 1994.

3. FDA Compliance Program Guidance Manual. Chapter 48: Human Drugs Bioresearch Monitoring. Program 7348.001, In Vivo Bioequilvalence. 1995.

4. Boyd, R.K., Henion, J.D., Alexander, M., Budde, W.L., Gilbert, J.D., Musser, S.M., Palmer, C. and Zurek, E.K. J. Am. Soc. Mass Spectrom. 1996, 7, 211- 218

ACKNOWLEDEMENTS

The Measurements and Standards Committee would like to thank the following individuals for their thoughtful comments and suggestions which added significantly to the quality of this document: P.K. Bennett, K. Chan, R.W. Edom, R.L. Foltz, P.J. Gale, J.D. Henion, S.M. Musser, T.D. Oglesby and T.V. Olah

SOP Example 1Generic Format

Analytical Services Lab ABC

Standard Operating Procedure

Title: Maintenance and Calibration of Mass Spectrometer Systems.

Procedure No.: INST0009.01 (Original)

Prepared by: Date:

Approved by: Date:

Effective Date: July 1995

Number of Pages: 4

This procedure becomes effective when approved by the Executive Director or appropriate Site Director. Approval of this page indicates approval of all pages in this procedure.

SOP INST0009.01

I. PURPOSE

The purpose of this document is to provide a standard operating procedure (SOP) for the maintenance and calibration of mass spectrometer systems in Analytical Services Lab ABC.

II. SCOPE AND IMPLEMENTATION

This SOP applies specifically to situations in which data obtained from a particular mass spectrometer system are to be used for registrational filings.

III. DEFINITIONS

A. Mass Spectrometer (MS) System: For the purposes of this SOP an MS system is defined as all components required to generate usable mass spectral-based data for a given sample. This includes but is not limited to all inlets (gas chromatograph, liquid chromatograph, solids probe, etc.), all electronics (power supplies, amplifiers, digital to analog converters, etc.), all hardware (lenses, mass analyzers, vacuum pumps, etc.) and all associated data system hardware and software.

B. Operator: Person or persons responsible for generating MS system data for a given sample or set of samples. C. Analytical method: Steps(s) to be followed for a given analysis of a given compound(s) in a given matrix,

including an outline of specific operational parameters for an MS system used in performing said analysis.

IV. RESPONSIBILITIES

A. It is the responsibility of the person(s) operating MS systems to follow this procedure.

B. It is the responsibility of the Director, Analytical Services Lab, to interpret this procedure.

V. PROCEDURES

A. Daily Procedures

MS settings appropriate for a given analysis of a given sample or sample set will be found in the analytical method for a given assay. Assessment of proper functioning of a given MS system in a given analytical run will be based on the performance of standards and quality control samples in that run.

Prior to analyzing samples on a specific MS system, it is recommended that the following items be checked. Critical parameters may be recorded in an electronic log maintained in the system's computer, in the laboratory notebook containing the data acquired or in the system's service log.

1. Vacuum system: pressures within normal range for that system.

2. Temperatures: temperature-controlled zones within normal range for the given MS system and for the given analytical method.

3. Mass axis calibration and resolution: axis calibration and resolution may be checked on an as-needed basis with either generic calibrants (PFTBA, Ultramarks, PPGs, etc.) which generate ions of known m/z ratios or with the compounds that are the subject(s) of the analysis. In all events, the calibrant should bracket the mass range of interest for a given analysis. The mass axis should be re-calibrated if the measured m/z of any of the calibrant ions in the range of interest differ by more than 0.15 amu from their expected mass. Resolution should be sufficient to discriminate all components of interest. Peak widths greater than 1 amu (measured at half height) should be used with caution. Special requirements for calibrants, mass range and resolution for a given assay should 'be specified in the analytical method.

4. Chromatographic inlets should be checked for required quantity and quality of carrier fluid and any leaks. Where found, deficiencies corrected prior to sample analysis.

5. Inlet injector assemblies, ion source assemblies, lens assemblies, etc. should be inspected and cleaned, if warranted by poor system performance, as indicated by poor mass peak shape/resolution and/or low sensitivity of calibrant or analyte.

6. If specified in the analytical method, a system suitability sample to test the entire MS system may be run prior to analyzing registrational sample(s). An

appropriate system suitability sample might be, but is not limited to, a low level standard from the analytical set to be run. In addition to whether sufficient sensitivity is available for the analysis, chromatographic peak shape and resolution (if appropriate) can be verified as well.

B. Annual Procedures

It is recommended that preventive maintenance be performed at 6-12 month intervals (or according to manufacturer's recommendations.)

1. Preventive maintenance items might include, but are not limited to, replacing vacuum pump fluids, changing gas adsorbers, cleaning mass analyzer assemblies and electronics bins, etc. (to be determined based on the manufacturer's recommendation for a given MS system.) Such maintenance is to be performed by an authorized individual, either a manufacturer's representative or another with suitable training or experience.

2. After completion of preventive maintenance, a test sample should be analyzed to verify system performance. This may either be a generic compound (PPGs, Ultramarks, etc.), or a specific compound whose performance is known to the operator.

VI. MANUALS

Manuals, which detail the specific operation of a specific MS system, are to be located where they are readily accessible to operators: either near the appropriate system or in a centralized library.

VII. TRAINING

MS system operators are to be familiar with all SOPs and operating manuals pertaining to the use of a given system.

VIII. DOCUMENTATION

A service log, maintained for each mass spectrometer system, will contain all service reports. Records of mass axis calibrations and any system suitability analyses will also be maintained, either in the service log or in the appropriate laboratory notebook that contains the data acquired with those calibrations. Archival storage of records shall follow SOP DOCU0009.02.

Example #2

Instrument Type Format

ANALYTICAL SERVICES LABORATORY DEF

STANDARD OPERATING PROCEDURE

Title: Use and Maintenance of a Tandem Triple

Quadrupole Mass Spectrometer

Procedure No.: INST0004.06

Supersedes

Procedure No.: INST0004.05

Prepared by: Date:

Approved by: Date:

Effective date: January 3, 1997

Number of pages: 6

Analytical Services Lab Standard Operating Procedure

SOP Number:

INST0004.06



Page 2 of 6 Effective date:

January 3, 1997

Supersedes SOP No.:

INST0004.05

Author's Initials/Date: Lab Director's Initials/Date:

I. PURPOSE

To provide general guidelines for conducting routine tandem triple quadrupole mass spectrometer operation and maintenance.

II. SCOPE AND IMPLEMENTATION

Adherence to this SOP is required for all tandem triple quadrupole mass spectrometric services offered by ABS that are subject to GLP guidelines.

III. INTRODUCTION AND DEFINITIONS

The mass spectrometer consists of a modern commercial quadrupole mass analyzing system that may be interfaced via an appropriate interface to a solution delivery system such as an infusion pump, a high performance liquid chromatograph or other condensed phase separation system including capillary electrophoresis instrumentation. The mass spectrometer is controlled by a data system that allows the operation of the mass spectrometer in all the appropriate modes required for analyses.

The mass spectrometer system is a highly sophisticated analytical instrument. It may be operated only by those who are conversant with the technique of mass spectrometry, have been trained in its operation and maintenance, and deemed competent by the Laboratory Director or designee. Routine operation of mass spectrometer systems are described in the operator's manual provided by the manufacturer.

Calibration: The process of calibrating the mass axis. This is performed using a

representative mass spectrum of a suitable reference compound (e.g., PPGs) recorded under experimental conditions appropriate for the analysis planned.

Tuning: The process of optimizing the mass spectrometer electronics (lens voltages

and resolution settings) for a particular compound(s).

IV. PROCEDURES

A. General Operation

The mass spectrometer system must be operated according to the procedures described in the appropriate operator manuals and/or according to updated practices accepted and demonstrated by this laboratory or by the manufacturer. The actual operation of the system depends on the analysis being carried out and the nature of the sample.


SOP Number:

INST0004.06




January 3, 1997

Supersedes SOP No.:

INST0004.05


B. Routine Mass Calibration

Mass axis calibration should be checked according to the procedures outlined below. This is performed using a representative mass spectrum of a suitable reference compound (e.g., PPGs) recorded under experimental conditions comparable to those used for the analysis planned for the study. Any deviations from expected mass assignments or sensitivity must be corrected by appropriate methods described in the operator' s manual (i.e., recalibration). A record of these data and the corresponding mass spectrometer conditions (e.g., lens

voltages, electron multiplier voltages, resolution settings) must be kept in the instrument calibration log binder.

For mass spectrometers that require a defrost cycle (recycle), a mass axis calibration check should be performed after a recycle, after maintenance that could affect calibration, prior to the initiation of a new project, and prior to performing a different analytical method on an instrument that has not been calibrated that day.

For mass spectrometers that do not require a recycle, a mass axis calibration check should be performed when changing projects and if the instrument has not been calibrated that day or after maintenance that could affect calibration. However, if a single method is being performed over more than one day, the instrument does not require a calibration check.

C. Non-Routine Mass Calibration

A mass-axis calibration that brackets the mass range of interest should be performed following non-routine maintenance by service engineers or by in-house trained operators. A full mass range calibration should also be performed at least annually or as indicated necessary by a performance check on a suitable reference mass standard (e.g., PPGs). The results of mass calibrations must be maintained in chronological instrument calibration log binders.

D. Data Collection

All data collection will be performed by the mass spectrometer's dedicated computer and data handling system. The operation of this system will be performed as recommended by the manufacturer as described in the instrument's operator manuals.


SOP Number:

INST0004.06




January 3, 1997

Supersedes SOP No.:

INST0004.05


E. Data Handling and Storage

All data stored on magnetic media or printed copies are to be maintained and retained according to SOP DOCU0003 and SOP COMP0005.

F. General Record Keeping

Periodic performance and maintenance records will be maintained in the mass spectrometer Maintenance and Calibration log book. A sample copy of information to be kept is shown in Appendix II.

G. Maintenance and Service

The mass spectrometer equipment will be maintained according to the procedures described in the manufacturer's Operator's Manual(s). Basic consumable spare parts will be held in the mass spectrometry laboratory. All spare parts may be obtained from the manufacturer or suitable alternative sources.

Routine preventive maintenance will be performed by a trained operator of the mass spectrometer system. When additional advice/expertise is required, the manufacturer's service department should be contacted. All Customer Service Reports should be retained in the Instrument Maintenance and Calibration log book.

In the event of malfunction or failure, non-routine maintenance may be performed. When

an instrument is found defective or out of specification, a notice shall be placed on it in clear view indicating that the instrument is not to be used until serviced and re-calibrated and found to be within specification. The notice shall indicate when service is expected. Records of repair must be documented and should include the nature of the problem or defect, how and when it was discovered and remedial action taken in response to the problem. This information should be documented in the instrument log.

H. Training

All personnel using the tandem triple quadrupole mass spectrometer will be trained by a qualified individual. Recurrency training will also be provided to ensure continued proper use of the mass spectrometer. All training will be documented and maintained in training records.

SOP INST0004

Appendix A: Revision History

Section and page of revision

Revision Revisor Date

I, page 2

II, page 2

III, page 2

IV.B, page 3

IV.C, page 3

IV.E, page 4

IV.F, page 5

IV.G, page 5

IV.H, page 5

Changed 'by which' to 'for conducting' Added 'tandem triple quadrupole mass spectrometric'

Changed 'provides for' to 'allows'

Renamed 'Routine Mass Calibration'

changed 'Maintenance and Calibration log book' to 'calibration log binder'

(Section IV.C also).

Renamed 'Non-Routine Mass Calibration', changed 'at least quarterly' to 'annually'.

Last two sentences revised.

Revised entire section.

J. Doe 5/5/95

Added

Added

IV.G, page 5 Added information on documentation of remedial action, placement of notice

J. Doe 12/4/95

III, page 2

IV.A, page 3

IV.C, page 3

IV.E, page 4

Appendix B, page 7

Deleted 'as well as non-routine' in 2nd paragraph.

'Validated' changed to 'demonstrated' in 1st sentence

Sentence 3 re-structured.

Added 'Quantitative' 1st sentence, deleted 'which covers this topic' 2nd paragraph. Removed sentence 'When a...'

Updated form

J. Doe 8/7/96

III, page 2

IV.B, page 3

IV.E, page 3

Added definitions of calibration and tuning

Defined requirements for recycled and non-recycled instruments

Revised section.

J. Doe 12/16/96

SOP INST0004

Appendix B

Mass Spectrometer Daily Performance Record

Operators Compound(s)

Interface

PSI He

(cyro)

PSI Ar

MaintenanceTime Temp

(K)Vacuum

(torr)Recycle Status

Base x10-5Initiated? Y/N

Monday Startam/pm x10-5 am/pm

Datepg. ref.

Finisham/pm x10-5 hrs./Auto

Operators Compound(s) PSI He

PSI Ar

MaintenanceTime Temp Vacuum Recycle

Interface (cyro) (K) (torr) Status


Tuesday Startam/pm x10-5 am/pm

Datepg. ref.



Interface

PSI He

(cyro)

PSI Ar


(K)Vacuum



Wednesday Startam/pm x10-5 am/pm

Datepg. ref.



Interface

PSI He

(cyro)

PSI Ar


(K)Vacuum



Thursday Startam/pm x10-5 am/pm

Datepg. ref.



Interface

PSI He

(cyro)

PSI Ar


(K)Vacuum



Friday Startam/pm x10-5 am/pm

Datepg. ref.


SOP Example #3Specific Instrument Format

STANDARD

OPERATING PROCEDURES

Analytical Services Lab GHI

10 Main St.

Analysisville, USA 1000

SOP NUMBER: LABEQ002.01

Page 1 of 6

TSQ 700, USE AND MAINTENANCE

This SOP is designed to provide general guidelines by which analysis and maintenance are conducted on the TSQ 700 Mass Spectrometer for projects conducted in support of regulatory filings. The TSQ 700 Mass Spectrometer is equipped with a DEC Station 5000/120 data system running Finnigan/MAT software. The TSQ 700 may be used with the following optional equipment:

1. Finnigan API/Electrospray interface

2. Gas Chromatograph - Varian

3. High Performance Liquid Chromatograph - Waters, HP

4. Desorption Chemical Ionization (DCI) Probe

The TSQ 700 mass spectrometer is a highly sophisticated analytical instrument. It may be operated only by those who are familiar with MS or MS/MS techniques and have been trained in its operation and maintenance.

General Operation: The MS is operated according to the procedures described in the appropriate Finnigan TSQ 700 manuals and/or according to updated practices accepted by this laboratory or by Finnigan. The precise operation of the MS depends on the analysis required and the nature of the sample. Although the operational procedures are not within the scope and requirements of this SOP, the following general procedures apply at all times.

Routine Start-up:

Pressures:

The pressure of the manifold should be recorded on the daily TSQ log sheet. Normal operating pressures (with GC flow but without CI or CID gases) should be< 2x10~ T. An increase in a half order of magnitude should be investigated for possible leaks. (If the source has been vented to atmosphere, it may take up to 4 days to reach ultimate vacuum pressures. However, the high voltage dynode may be turned on when the manifold pressure is < 2x10-5 T

Check for sufficient gas tank pressures.

Check for appropriate pressure of CI reagent gas. Typical source pressure with ammonia reagent gas is about 5000 mT,

or set the pressure as indicated in the method SOP.

Temperatures: The manifold temperature is normally set at 750C and should be checked prior to use. The source temperature should be set for the operation being performed.

Data System: Normally the data system is on. Change to the appropriate subdirectory for

collection of data.

Effective 6/5/96

STANDARD



10 Main St.



Page 2 of 6

Calibration checks - Routine: On each day of analysis, the masses of interest of the analyte should be recorded to ensure satisfactory calibration of the instrument. Alternatively, a spectrum of the tuning solution (i.e. pftba, MRFA) may be collected if it covers the range of the masses being analyzed. Calibration checks should be documented in the daily log as acceptable if within + 0.2 amu of the expected mass.

Instrument Use: At the beginning of an analytical batch, a clean ion volume is inserted as needed and the instrument tune is checked and/or adjusted. The tune is considered acceptable if sensitivity and specificity is adequate for the assay. (Resolution should be a minimum of 2 amu for Q1 and 1.5 amu for Q3.) Analysis of a given sample or batch of samples should only proceed as long as the performance of the TSQ 700 is suitable for analysis. (Refer to performance checks in SOP LABOP006 &/or specific method SOPs.)

Data Handling and Storage: Data is initially collected on the DEC Station hard disk. Hard copy printouts are made of pertinent information (chromatograms, quantitations). Computer data on the DEC hard disk is backed up onto magnetic storage tapes for archival.

Maintenance and Service: The equipment will be maintained according to the procedures described in the appropriate TSQ 700 Operator's manual. Routine preventative maintenance and minor repairs can be performed by a trained operator. When additional advice/expertise is required, contact Finnigan Service. A11 Customer Service Reports are retained. A schedule of routine maintenance procedures is found in Appendix A.

RF Adjustment & Coarse Mass Calibration - Non Routine: A mass calibration should be performed by Finnigan engineers or by in-house trained operators according to the Finnigan Operator's Manual following non-routine maintenance. A coarse mass calibration and RF adjustment should also be performed whenever the instrument is altered, i.e., if the source/quads are physically altered as in removal for cleaning or change in ionization techniques.

General Record Keeping: Instrument routine operation and maintenance, daily & weekly, will be logged by a qualified operator (see example form 'MSMaintO1' in appendix B), kept in the "TSQ 700 Log Book". Other routine/non-routine maintenance and repair records will also be kept in the TSQ 700 log book, (see example form 'TSQ maint 02 in Appendix C). Maintenance/repair of the associated turbo pump, rough pumps and data system are recorded (see example maintenance form "GenO1", Appendix D). Calibration records are maintained in the calibration file. A chronological log of unexpected problems and corrective actions is also kept.

Effective 6/5/96

STANDARD



10 Main St.



Page 3 of 6

Appendix A, TSQ 700 Routine, Preventative Maintenance

Daily*: Check pressures.

Check for air leaks

Check calibration

*Daily means each day of use

Monthly: Check RF tune

Quarterly: Change rough pump oil

Clean card cage fan filters

6-9 months: Change turbo pump oil

12-15 months: Clean Q1

Every 3 years or as needed: Clean Q3

As needed: Replace or clean ion volume. Generally at the start of an analytical batch.

Clean lens and source block

Replace filament

Tuning and calibration

Ballast (purge) rough pump. For example, it is needed when large amounts of volatile liquids are being pumped or bubbles are seen in pump oil.

Effective 6/5/96

STANDARD



10 Main St.


Page 4 of 6


Appendix B

Daily Log of Routine Maintenance and Checks

Instrument:

Month Pressure tuned calib ck cleaning Comments

Day Init. Ion Type

Manifold (Torr)

pftba other, specify

accept y/n

cmpdion vol

API spray shield

heated capillary

Effective 6/5/96

STANDARD



10 Main St.



Page 5 of 6

Appendix C

Maintenance/Repair Log

Date Filament _

Lens Cleaned, as needed

Block Cleaned, as needed

Clean Q1, 12-15 mo

Other Maintenance or Repair Performed / Comments

Effective 6/5/96

STANDARD



10 Main St.



Page 6 of 6

Appendix D

Maintenance / Repair Log

Equipment:

Location:

Serial# / ID:

Routine Maintenance:

Date Routine

(Y/N)

Maintenance or Repair Performed Comments

SOP Example #4Instrument type format with separate method

specific instrument operation procedures

Standard Operating Procedure Document# AI.001

Revision B

Title: Tuning and Calibration of Quadrupole Mass Spectrometers

Preparation Date: 8/11/96

Effective Date: 8/17/96

Page 1 of 3

1.0 Purpose

The purpose of this SOP is to define generalized procedures for tuning and calibration of quadrupole mass spectrometer analytical systems.

2.0 Scope

This SOP pertains to tuning which is performed to establish and/or verify proper calibration, resolution and ion transmission of the instrument and defines when such activities are warranted and required. More specific tuning and calibration are method, instrument and interface dependent and are included in Test Method SOPs. Tuning and calibration may be performed only by trained persons who have demonstrated proficiency in training module L4007.

3.0 Responsibilities:

The proper tuning and calibration of the instrument is the responsibility of the user. For quantitative work, the user is the operator who evaluates the system suitability criteria specified in each Test Method before beginning an analytical sequence. For qualitative work, the user is the qualified operator performing the analyses and is identified in the System Log.

Prepared By Date

Management Date

Quality Assurance Date

AI.001.B Quadrupole Tuning and Calibration Page 2 of 3

4.0 Operation

4.1 Requirements for Tuning and Calibration

4.1.1 Circumstances That Require Tuning and Calibration of a Validated Quadrupole Mass Spectrometer System

Before starting the validation of a quantitative assay.

Before starting qualitative analysis on a regulated study (as indicated in the RFA).

When Test Method specific system suitability samples fail to meet the tolerances of analyzer related criteria.

If the mass spectrometer is vented and physical manipulation of the ion optics is performed, such as cleaning lenses or removal and cleaning of the quadrupole assemblies.

If the RF parameters are modified.

If the electronic components that effect calibration, resolution and detection are changed. These include DC Rod Driver, Phase Lock Loop, RF Amplifier, and RF Detector components.

4.1.2 Circumstances That Do Not Require Tuning and Calibration

If changing from ESI to APCI (verify the system performance using a system suitability standard).

If the system is vented to clean the API skimmer, tube lens and heated capillary, only (verify the system performance using a system suitability standard).

Changing the filament or ion volume in EI/CI operation.

4.2 Application Specific Tuning

4.2.1 System Tuning and Calibration For Electron Impact (EI) and Positive/Negative Chemical Ionization (CI)

Tuning and calibration is performed on the generic calibrant FC-43 (perfluorotributylamine). For full scan MS or MS/MS evaluation of complex mixtures or molecular determinations, the system is tuned at unit resolution and calibrated to the exact masses listed below (1 0.05 amu). For Test Methods using EI/CI, other tuning requirements are outlined in the specific SOP.

AI.001.B Quadrupole Tuning and Calibration Page 3 of 3

EI Tune and Calibration Masses

68.995, 130.992, 218.986, 413.978, 501.971, 613.965.

Positive Methane CI Tune and Calibration Masses

68.995, 130.992, 218.986, 413.978, 501.971, 651.962.

Negative Methane CI Tune and Calibration Masses

168.989, 282.985, 413.978, 556.969, 632.963

4.2.2 Positive/ Negative Ion Electrospray (ESI) and Atmospheric Pressure Ionization (APCI) For LC/MS and Molecular Weight Determinations

A tuning solution containing Benzophenone, Adenosine and Erythromycin, each at 100 ng/5L, is infused and used to tune and calibrate at the protonated

masses 183.081, 268.105, and 716.469, respectively (1 0.05 amu), at unit resolution.

For negative ion tuning, selected parameters of the current positive ion tune table are copied and/or inverted to the negative ion tune table. Tuning and calibration are verified using a 100 ng/5L solution of Estrone-3-sulfate, molecular ion 349.111 (1 0.05 amu).

4.2.3 Electrospray Ionization (ESI) of Peptides and Tryptic Digests

For the analysis of tryptic digests and peptides, refer to TM.064 (“Analysis of Peptide Digests”).

4.2.4 Electrospray Ionization (ESI) of Proteins and Biomolecules

The instrument is tuned and calibrated for single quadrupole evaluation of proteins and biomolecules using a solution containing 5 pmol/5L of myoglobin and 20 pmol/5L MRFA to the known average masses for myoglobin (848.5, 1060.4, 1211.8, 1413.5, 1696.0 ) and for MRFA (262.6, 524.3). The calibration is verified by acquiring a 2 minute signal averaged spectrum. The average spectrum is deconvoluted and must be with 10.01% of 16,951 da.

4.3 Tuning and Calibration Documentation

Upon completion of tuning and calibration, the tune table is stored to disk and documentation of the tune is entered in the System Log.

Sections of a Specific Test Method pertaining to MS setup, tuning and calibration

3.6 Mass Spectral Analyses

Mass spectra are acquired and recorded with a standard Finnigan TSQ-700 (Finnigan Corp., San Jose, CA) equipped with the standard ESI source manufactured and distributed by Finnigan. The following are experimentally determined ranges or specified settings. Final values within the ranges are determined by the optimization of the ion current.

Electrospray Voltage: 4.5 kV

Heated Capillary Setting: 225 C

Nebulizing Gas Flow: 70-90psig

Auxiliary Gas Flow: 10-20 (flowmeter reading)

Argon Collision Gas Pressure: Adjust manifold pressure to 2.5 - 2.7 x 10-5 Torr

Collision Energy: 27 eV

Conversion Dynode Voltage: -12 to -18 kV

Secondary Electron Multiplier Setting: 800-2000 V

Tuning and calibrating is done by infusing a solution of 10.0 5g/mL of XYZ-988 at 5 5L/min into the mobile phase stream (80% B at 0.2 mL/min). The protonated parent ion mass for XYZ-988 is 474.2. Correct calibration of 474.2 (1 0.1 amu) is established in the profile mode for Q1 at unit resolution (FWHM approximately 0.65 amu). Similarly, Q3 is calibrated at unit resolution in the Daughter mode at product mass 290.1 (1 0.1 amu). The frequency of tuning and calibration is determined by system suitability standards (see Section 4.0).

Analyses are performed in selected reaction monitoring (SRM) mode using an ICL procedure "tm050" (see TM.050 test method file). The precursor/product transitions used for each SRM scan are shown below. The scanning quadrupole of the mass spectrometer (Q3) scans a 0.3 amu window centered around the product ion of interest. The scan time for each SRM scan is set to 0.3 seconds resulting in a total cycle time of approximately 0.6 seconds.

Component Precursor Ion Product Ion

XYZ-988 474.2 290.1

d5-XYZ-988 479.2 295.1

Examples of chromatograms obtained from blank plasma, low, and high calibrators are on file in the TM.050 test method file.

4.0 In-process Validation Criteria:

The system is normally prepared for an analytical run by checking with a 1.00 ng/mL unextracted analytical standard (system suitability standard). Upon injection, the sample must yield the following results before proceeding with the analytical run:

1) Chromatographic peak widths < 10 seconds.

2) S/N on analyte > 15:1

3) Area ratio between 0.025 and 0.030 for xyz-988

4) Retention time between 4.6 and 4.8 min.

If the system fails to meet these criteria, appropriate action (e.g. tuning) should be taken to rectify the deficiency and the system suitability standard reanalyzed. Correct performance of the system suitability standard is documented in the System Log.

Documents

Guidelines for Writing an SOP for Mass Spectrometryba333.free.fr/khira/Guidelines for Writing an SOP for... · Web viewGuidelines for Writing an SOP for Mass Spectrometry prepared