Test Catalog

Test Id : CLZ

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Clozapine, Serum

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Overview

Test Catalog

Useful For
Suggests clinical disorders or settings where the test may be helpful

Monitoring patient compliance of clozapine treatment

 

An aid to achieving desired serum levels

Method Name
A short description of the method used to perform the test

Liquid Chromatography Tandem Mass Spectrometry (LC-MS/MS)

NY State Available
Indicates the status of NY State approval and if the test is orderable for NY State clients.

Yes

Reporting Name
Lists a shorter or abbreviated version of the Published Name for a test

Clozapine, S

Aliases
Lists additional common names for a test, as an aid in searching

Clozapine (Clozaril)

Clozaril (Clozapine)

Specimen Type
Describes the specimen type validated for testing

Serum Red

Specimen Required
Defines the optimal specimen required to perform the test and the preferred volume to complete testing

Supplies: Sarstedt Aliquot Tube, 5 mL (T914)

Collection Container/Tube: Red top (serum gel/SST are not acceptable)

Submission Container/Tube: Plastic vial

Specimen Volume: 1 mL

Collection Instructions:  

1. Collect specimen immediately before next scheduled dose.

2. Within 2 hours of collection, centrifuge and aliquot serum into a plastic vial.

Additional Information: Therapeutic range (trough level) applies to specimens collected immediately prior to next dose.

Forms

If not ordering electronically, complete, print, and send a Therapeutics Test Request (T831) with the specimen.

Specimen Minimum Volume
Defines the amount of sample necessary to provide a clinically relevant result as determined by the testing laboratory. The minimum volume is sufficient for one attempt at testing.

0.6 mL

Reject Due To
Identifies specimen types and conditions that may cause the specimen to be rejected

Gross hemolysis OK
Gross lipemia OK
Gross icterus OK

Specimen Stability Information
Provides a description of the temperatures required to transport a specimen to the performing laboratory, alternate acceptable temperatures are also included

Specimen Type Temperature Time Special Container
Serum Red Refrigerated (preferred) 28 days
Frozen 28 days
Ambient 7 days

Useful For
Suggests clinical disorders or settings where the test may be helpful

Monitoring patient compliance of clozapine treatment

 

An aid to achieving desired serum levels

Clinical Information
Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

Clozapine (Clozaril), a tricyclic dibenzodiazepine, is used for the symptomatic management of psychotic disorders and is considered an atypical antipsychotic drug. It is currently used primarily for the treatment of patients with schizophrenia or schizoaffective disorders who are at risk for recurrent suicidal behavior and who have encountered nonresponse or adverse, intolerable extrapyramidal side effects with more classical antipsychotics (chlorpromazine, haloperidol).

 

Although clozapine was developed about 30 years ago and the initial results were promising, the development of several fatal cases of agranulocytosis resulted in the discontinued use of this agent. Seizures, orthostatic hypotension, and an increased risk of fatal myocarditis have also been associated with the use of clozapine. The use of clozapine has regained interest for several reasons. Patients who did not respond to treatment with other antipsychotics improved when clozapine was administered. Also, agranulocytosis, which occurs in approximately 1% to 2% of patients, can be controlled with close hematologic monitoring. However, because of the significant risk of agranulocytosis and seizure associated with its use, clozapine should only be used in patients who have failed to respond adequately to treatment with appropriate courses of standard drug treatments, either because of insufficient effectiveness or the inability to achieve an effective dose because of intolerable adverse reactions from those drugs.

 

Treatment is usually started with dosages of 25 to 75 mg/day with a gradual increase to reach a final dose of 300 to 450 mg/day within approximately 2 weeks of the initiation of treatment. Once the desired effect is achieved, the dose may be gradually decreased to keep the patient on the lowest possible effective dose.

 

Patients being treated with clozapine should be closely monitored during treatment for adverse reactions. Treatment must include monitoring of white blood cell count and absolute neutrophil count. Clozapine treatment should be discontinued in patients failing to show an acceptable clinical response. In addition, the need for continuing treatment should be periodically reevaluated in patients exhibiting beneficial clinical responses.

 

Clozapine is metabolized to desmethylated and N-oxide derivatives. The desmethyl metabolite (norclozapine) has only limited activity, and N-oxide metabolite is inactive.

Reference Values
Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

Clozapine

Therapeutic range: 350-600 ng/mL

 

Norclozapine

Therapeutic range: Not well established

 

Clozapine + Norclozapine

Therapeutic range: Not well established

Interpretation
Provides information to assist in interpretation of the test results

The effectiveness of clozapine treatment should be based on clinical response and treatment should be discontinued in patients failing to show an acceptable clinical response.

Cautions
Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

No significant cautionary statements

Clinical Reference
Recommendations for in-depth reading of a clinical nature

1. Volpicelli SA, Centorrino F, Puopolo PR, et a,: Determination of clozapine, norclozapine, and clozapine-N-oxide in serum by liquid chromatography. ClinChem. 1993;39(8):1656-1659

2. Chung MC, Lin SK, Chang WH, Jann MW. Determination of clozapine and desmethylclozapine in human plasma by high-performance liquid chromatography with ultraviolet detection. J Chromatogr. 1993;613(1):168-173. doi:10.1016/0378-4347(93)80212-m

3. Perry PJ, Miller DD, Arndt SV, Cadoret RJ. Clozapine and norclozapine plasma concentrations and clinical response of treatment-refractory schizophrenia patients. Am J Psychiatry. 1991;148(2):231-235. doi:10.1176/ajp.148.2.231

4. Physicians' Desk Reference (PDR). 61st ed. Thomson PDR; 2007

5. Fitton A, Heel RC. Clozapine. A review of its pharmacological properties, and therapeutic use in schizophrenia. Drugs. 1990;40(5);722-747. doi:10.2165/00003495-199040050-00007

6. Clozaril. Package insert: Novartis Pharmaceuticals; 05/2005

7. Mitchell PB. Therapeutic drug monitoring of psychotropic medications. Br J Clin Pharmacol. 2001;52(Suppl 1):45S-54S. doi:10.1046/j.1365-2125.2001.0520s1045.x

8. Hiemke C, Bergemann N, Clement HW, et al. Consensus Guidelines for Therapeutic Drug Monitoring in Neuropsychopharmacology: Update 2017. Pharmacopsychiatry. 2018;51(1-02):9-62. doi:10.1055/s-0043-116492

9. Milone MC, Shaw LM: Therapeutic drugs and their management. In: Rifai N, Chiu RWK, Young I, Burnham CAD, Wittwer CT, eds. Tietz Textbook of Laboratory Medicine. 7th ed. Elsevier; 2023:420-453

Method Description
Describes how the test is performed and provides a method-specific reference

Deuterated stable isotope of clozapine is added to the serum sample as an internal standard. Protein is precipitated from the mixture by the addition of acetonitrile. Clozapine, norclozapine, and the internal standard are extracted from the resulting supernatant by an online extraction utilizing high-throughput liquid chromatography. This is followed by conventional liquid chromatography and analysis on a tandem mass spectrometer equipped with a heated nebulizer ion source.(Unpublished Mayo method)

PDF Report
Indicates whether the report includes an additional document with charts, images or other enriched information

No

Day(s) Performed
Outlines the days the test is performed. This field reflects the day that the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time before the test is performed. Some tests are listed as continuously performed, which means that assays are performed multiple times during the day.

Monday through Friday

Report Available
The interval of time (receipt of sample at Mayo Clinic Laboratories to results available) taking into account standard setup days and weekends. The first day is the time that it typically takes for a result to be available. The last day is the time it might take, accounting for any necessary repeated testing.

3 to 5 days

Specimen Retention Time
Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded

2 weeks

Performing Laboratory Location
Indicates the location of the laboratory that performs the test

Rochester

Fees
Several factors determine the fee charged to perform a test. Contact your U.S. or International Regional Manager for information about establishing a fee schedule or to learn more about resources to optimize test selection.

  • Authorized users can sign in to Test Prices for detailed fee information.
  • Clients without access to Test Prices can contact Customer Service 24 hours a day, seven days a week.
  • Prospective clients should contact their account representative. For assistance, contact Customer Service.

Test Classification
Provides information regarding the medical device classification for laboratory test kits and reagents. Tests may be classified as cleared or approved by the US Food and Drug Administration (FDA) and used per manufacturer instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR) product.

This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. It has not been cleared or approved by the US Food and Drug Administration.

CPT Code Information
Provides guidance in determining the appropriate Current Procedural Terminology (CPT) code(s) information for each test or profile. The listed CPT codes reflect Mayo Clinic Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.

CPT codes are provided by the performing laboratory.

80159

LOINC® Information
Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the order and results codes of this test. LOINC values are provided by the performing laboratory.

Test Id Test Order Name Order LOINC Value
CLZ Clozapine, S 65632-2
Result Id Test Result Name Result LOINC Value
Applies only to results expressed in units of measure originally reported by the performing laboratory. These values do not apply to results that are converted to other units of measure.
33841 Norclozapine 10992-6
33842 Clozapine+Norclozapine Total 12375-2
33840 Clozapine 6896-5

Test Setup Resources

Setup Files
Test setup information contains test file definition details to support order and result interfacing between Mayo Clinic Laboratories and your Laboratory Information System.

Excel | Pdf

Sample Reports
Normal and Abnormal sample reports are provided as references for report appearance.

Normal Reports | Abnormal Reports

SI Sample Reports
International System (SI) of Unit reports are provided for a limited number of tests. These reports are intended for international account use and are only available through MayoLINK accounts that have been defined to receive them.

SI Normal Reports | SI Abnormal Reports