Immunoassay in healthcare testing applications

Authors

  • Anne Z. DePriest, PharmD, BCPS
  • David L. Black, PhD, D-ABFT
  • Timothy A. Robert, PhD, D-ABCC

Keywords:

immunoassay, urine drug testing, pain management, screening

Abstract

Immunoassay is used extensively for drug testing in pain management. Drug testing for the purpose of compliance monitoring is fundamentally different from forensic applications, which may rely on immunoassay screening to rapidly identify “negative” samples. In clinical settings, focus is shifted from identification of select drugs of abuse with low positivity rates to detection of a wide variety of licit and illicit compounds with expected high positivity rates. The primary drug classes of interest in this population, opioids and benzodiazepines, require special testing considerations when immunoassay is used. This review highlights the performance characteristics of immunoassay, with special emphasis on prescription drug classes and testing at the point-of-care.

Author Biographies

Anne Z. DePriest, PharmD, BCPS

Aegis Sciences Corporation, Nashville, Tennessee; College of Pharmacy, University of Tennessee, Memphis, Tennessee.

David L. Black, PhD, D-ABFT

Aegis Sciences Corporation, Nashville, Tennessee; Department of Pathology, Immunology and Microbiology, Vanderbilt University, Nashville, Tennessee.

 

Timothy A. Robert, PhD, D-ABCC

Aegis Sciences Corporation, Nashville, Tennessee.

References

Berson SA, Yalow RS: Quantitative aspects of the reaction between insulin and insulin-binding antibody. J Clin Invest. 1959; 38: 1996-2016.

Yalow RS, Berson SA: Assay of plasma insulin by immunological methods. Nature. 1959; 184: 1648-1649.

Smith ML: Immunoassay. In Levine B (ed.): Principles of Forensic Toxicology. 4th ed. Washington, DC: AACC Press, 2013: 149-169.

DePriest AZ: Drug testing in pain management. In Levine B (ed.): Principles of Forensic Toxicology. 4th ed. Washington, DC: AACC Press, 2013: 61-75.

Substance Abuse and Mental Health Services Administration: Clinical drug testing in primary care. Technical Assistance Publication (TAP) 32. HHS Publication No. (SMA) 12-4668. Rockville, MD: Substance Abuse and Mental Health Services Administration, 2012.

Gourlay DL, Heit HA, Caplan YH: Urine drug testing in clinical practice: The art and science of patient care. 4th ed. Baltimore, MD: The Johns Hopkins University School of Medicine, 2012: 1-24.

Centers for Disease Control and Prevention: Clinical Laboratory Improvement Amendments. Title 42, Chapter IV, Centers for Medicare & Medicaid Services, Department of Health and Human Services. Subchapter G – Standards and Certification. Available at http://www.gpo.gov/fdsys/pkg/CFR-2003-title42-vol3/xml/CFR-2003-title42-vol3-part493.xml. Accessed October 14, 2013.

US Food and Drug Administration: CLIA-Clinical Laboratory Improvement Amendments. Available at http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfCLIA/search.cfm. Accessed October 14, 2013.

Substance Abuse and Mental Health Services Administration: Center for Behavioral Health Statistics and Quality. Treatment Episode Data Set (TEDS): 2000-2010. National Admissions to Substance Abuse Treatment Services. DASIS Series S-61, HHS Publication No. (SMA) 12-4701. Rockville, MD: Substance Abuse and Mental Health Services Administration, 2012.

Reisfield GM, Salazar E, Bertholf RL: Rational use and interpretation of urine drug testing in chronic opioid therapy. Ann Clin Lab Sci. 2007; 37(4): 301-314.

Department of Health and Human Services: Revised mandatory guidelines for federal workplace drug testing programs. Fed Regist. 1994; 59: 29908-29931.

Department of Health and Human Services: Mandatory guidelines for federal workplace drug testing programs. Fed Regist. 1997; 62: 51118-51120.

Melanson SF: Drug-of-abuse testing at the point of care. Clin Lab Med. 2009; 29: 503-509.

Peace MR, Tarnai LD, Poklis A: Performance evaluation of four on-site drug-testing devices for detection of drugs of abuse in urine. J Anal Toxicol. 2000; 24: 589-594.

Luzzi VI, Saunders AN, Koenig JW, et al.: Analytic performance of immunoassays for drugs of abuse below established cutoff values. Clin Chem. 2004; 50: 717-722.

Mitchell JM: Immunoassays as an initial test in drug testing. RTI International. Presented at the Substance Abuse and Mental Health Services Administration (SAMHSA) Drug Testing Advisory Board (DTAB). August 2008.

Stout PR, Klette KL, Horn CK: Evaluation of ephedrine, pseudoephedrine, and phenylpropanolamine concentrations in human urine samples and a comparison of the specificity of DRI amphetamines and Abuscreen online (KIMS) amphetamines screening immunoassays. J Forensic Sci. 2004; 49: 160-164.

Phan HM, Yoshizuka K, Murry DJ, et al.: Drug testing in the workplace. Pharmacotherapy. 2012; 32: 649-656.

Strano-Rossi S, Leone D, de la Torre X, et al.: The relevance of the urinary concentration of ephedrines in anti-doping analysis: Determination of pseudoephedrine, cathine, and ephedrine after administration of over-the-counter medicament. Ther Drug Monit. 2009; 31: 520-526.

DePriest AZ, Knight JL, Doering PL, et al.: Pseudoephedrine and false-positive immunoassay urine drug tests for amphetamine. Pharmacotherapy. 2013; 33(5): e88-e89.

Moeller KE, Lee KC, Kissack JC: Urine drug screening: practical guide for clinicians. Mayo Clin Proc. 2008; 83(1): 66-76.

Passik SD, Heit H, Rzetelny A, et al.: Trends in drug and illicit use from urine drug testing in addiction treatment clients. Presented at the Proceedings of the International Conference on Opioids, Boston, MA, 2013.

Manchikanti L, Malla Y, Wargo BW, et al.: Comparative evaluation of the accuracy of immunoassay with liquid chromatography tandem mass spectrometry (LC/MS/MS) of urine drug testing (UDT) opioids and illicit drugs in chronic pain patients. Pain Physician. 2011; 14: 175-187.

Dietzen DJ, Ecos K, Friedman D, et al.: Positive predictive values of abused drug immunoassays on the Beckman Synchron in a veteran population. J Anal Toxicol. 2001; 25: 174-178.

Ferrara SD, Tedeschi L, Frison G, et al.: Drugs-of-abuse testing in urine: Statistical approach and experimental comparison of immunochemical and chromatographic techniques. J Anal Toxicol. 1994; 18: 278-291.

Reisfield GM, Goldberger BA, Bertholf RL: ‘False-positive’ and ‘false-negative’ test results in clinical urine drug testing. Bioanalysis. 2009; 1(5): 937-952.

Brahm NC, Yeager LL, Fox MD, et al.: Commonly prescribed medications and potential false-positive urine drug screens. Am J Health-Syst Pharm. 2010; 67: 1344-1350.

Collins AA, Merritt AP, Bourland JA: Cross-reactivity of tapentadol specimens with DRI methadone enzyme immunoassay. J Anal Toxicol. 2012; 36: 582-587.

Cotten SW, Duncan DL, Burch EA, et al.: Unexpected interference of baby wash products with a cannabinoid (THC) immunoassay. Clin Biochem. 2012; 45: 605-609.

Zacher JL, Givone DM: False-positive urine opiate screening associated with fluoroquinolone use. Ann Pharmcother. 2004; 38: 1525-1528.

Baden LR, Horowitz G, Jacoby H, et al.: Quinolones and false-positive urine screening for opiates by immunoassay technology. JAMA. 2001; 286: 3115-3119.

Wyeth Pharmaceuticals Inc.: Protonix Prescribing Information. Philadelphia, PA: Wyeth Pharmaceuticals Inc., May 2008.

Blank A, Hellstern V, Schuster D, et al.: Efavirenz treatment and false-positive results in benzodiazepine screening tests. Clin Infect Dis. 2009; 48(12): 1787-1789.

Heltsley R, Zichterman A, Black DL, et al.: Urine drug testing of chronic pain patients. II. Prevalence patterns of prescription opiates and metabolites. J Anal Toxicol. 2010; 34(1): 32-38.

DePriest A, Heltsley R, Black DL, et al.: Urine drug testing of chronic pain patients. III. Normetabolites as biomarkers of synthetic opioid use. J Anal Toxicol. 2010; 34: 444-449.

Owen GT, Burton AW, Schade CM, et al.: Urine drug testing: current recommendations and best practices. Pain Physician. 2012; 15: ES119-ES133.

Von Seggern RL, Fitzgerald CP, Adelman LC, et al.: Laboratory monitoring of OxyContin (oxycodone): Clinical pitfalls. Headache. 2004; 44: 44-47.

Bertol E, Vaiano F, Borsotti M, et al.: Comparison of immunoassay screening tests and LC-MS-MS for urine detection of benzodiazepines and their metabolites: Results of a national proficiency test. J Anal Toxicol. 2013; 37: 659-664.

Siemens Healthcare Diagnostics, Inc.: EMIT Drugs of Abuse Urine Assays Cross-Reactivity List. Deerfield, IL: Siemens Healthcare Diagnostics, Inc., 2008.

Innovacon, Inc.: CLIA Waived Multi-CLIN™ Drug Screen Test Device. San Diego, CA: Innovacon, Inc., 2008-02-27.

Alfa Scientific Designs, Inc.: Instant-View Multi-Drug Screen Urine Test. Poway, CA: Alfa Scientific Designs, Inc., 6/13 2007.

Branan Medical Corporation: QuickTox Drug Screen Dipcard Quick Reference Guide. Irvine, CA, Branan Medical Corporation, July 2008.

American Screening Corporation: Reveal Multi-Drug Testing Cup. Shrevepoint, LA: American Screening Corporation, 8/2010.

Cone EJ, Caplan YH, Black DL, et al.: Urine drug testing of chronic pain patients: Licit and illicit drug patterns. J Anal Toxicol. 2008; 32: 530-543.

Bartholow M: Top 200 drugs of 2012. Pharmacy Times. July 17, 2013. Available at http://www.pharmacytimes.com/publications/issue/2013/July2013/Top-200-Drugs-of-2012. Accessed October 17, 2013.

Valtier S, Bebarta VS: Excretion profile of hydrocodone, hydromorphone and norhydrocodone in urine following single dose administration of hydrocodone to healthy volunteers. J Anal Toxicol. 2012; 36: 507-514.

Cone EJ, Heltsley R, Black DL, et al.: Prescription opioids. I. Metabolism and excretion patterns of oxycodone in urine following controlled single dose administration. J Anal Toxicol. 2013; 37: 255-264.

Cone EJ, Heltsley R, Black DL, et al.: Prescription opioids. II. Metabolism and excretion patterns of hydrocodone in urine following controlled single-dose administration. J Anal Toxicol. 2013; 37: 486-494.

Lee HK, Lewis LD, Tsongalis GJ, et al.: Negative opioid screening caused by rifampin-mediated induction of oxycodone hepatic metabolism. Clin Chim Acta. 2006; 367: 196-200.

Cytochrome P450 Drug Interactions. Pharmacist's Letter/Prescriber's Letter. 2006; 22(2): 220233 [Full update October 2009; last modified November 2011].

Moody DE, Liu F, Fang WB: In vitro inhibition of methadone and oxycodone cytochrome P450-dependent metabolism: Reversible inhibition by H2-receptor agonists and proton-pump inhibitors. J Anal Toxicol. 2013; 37: 476-485.

Indiana University Department of Medicine: Cytochrome P450 Drug Interaction Table. 2003. Available at http://medicine.iupui.edu/clinpharm/ddis/p450_Table_Oct_11_2009.pdf. Accessed April 23, 2012.

Baselt RC: Disposition of Toxic Drugs and Chemicals in Man. 9th ed. Foster City, CA: Chemical Toxicology Institute, 2011.

deRienz RT, Holler JM, Manos ME, et al.: Evaluation of four immunoassay screening kits for the detection of benzodiazepines in urine. J Anal Toxicol. 2008; 32: 433-437.

Phillips JE, Bogema S, Fu P, et al.: Signify ER Drug Screen Test evaluation: Comparison to Triage Drug of Abuse Panel plus tricyclic antidepressants. Clin Chim Acta. 2003; 328(1- 2):31-38.

Way BA, Walton KG, Koenig JW, et al.: Comparison between the CEDIA and EMIT II immunoassays for the determination of benzodiazepines. Clin Chim Acta. 1998; 271: 1-9.

West R, Pesce A, West C, et al.: Comparison of clonazepam compliance by measurement of urinary concentration by immunoassay and LC/MS/MS in pain management population. Pain Physician. 2010; 13: 71-78.

Dasgupta A: The effects of adulterants and selected ingested compounds on drugs-of-abuse testing in urine. Am J Clin Pathol. 2007; 128: 491-503.

Mikel C, Almazan P, West R, et al: LC-MS/MS extends the range of drug analysis in pain patients. Ther Drug Monit. 2009; 31: 746-748.

Pesce A, West C, West R, et al.: Determination of medication cutoff values in a pain patient population. J Opioid Manage. 2011; 7: 117-122.

Pesce A, Rosenthal M, West R, et al.: An evaluation of the diagnostic accuracy of liquid chromatography-tandem mass spectrometry versus immunoassay drug testing in pain patients. Pain Physician. 2010; 13: 273-281.

Warner A: Interference of common household chemicals in immunoassay methods for drugs of abuse. Clin Chem. 1989; 35(4): 648-651.

Leino A, Saarimies J, Gronholm M, et al.: Comparison of eight commercial on-site screening devices for drugs-of-abuse testing. Scand J Clin Lab Invest. 2001; 61(4): 325-331.

de la Torre R, Domingo-Salvany A, Badia R, et al.: Clinical evaluation of the triage analytic device for drugs-of-abuse testing. Clin Chem. 1996; 42(9): 1433-1438.

Taylor EH, Pizzo P: Evaluation of the DrugCheck 9 on-site immunoassay test cup according to a standard method validation protocol. J Anal Toxicol. 2004; 28(3): 190-197.

Manchikanti L, Malla Y, Wargo BW, et al.: Protocol for accuracy of point-of-care (POC) or in-office urine drug testing (immunoassay) in chronic pain patients: A prospective analysis of immunoassay and liquid chromatography tandem mass spectrometry (LC/MS/MS). Pain Physician. 2010; 13(1): E1-E22.

Peppin JF, Passik SD, Couto JE, et al.: Recommendations for urine drug monitoring as a component of opioid therapy in the treatment of pain. Pain Med. 2012; 13: 886-896.

Federation of State Medical Boards. Model policy on the use of opioid analgesics in the treatment of chronic pain. July 2013. Available at http://www.fsmb.org/pdf/pain_policy_july2013.pdf. Accessed October 17, 2013.

DePriest A, Black DL, Robert T, et al.: Interpretation of urine specimens containing prescription drugs without metabolites: Adulteration, impaired metabolism or normal excretion? Presented at the Society of Forensic Toxicologists Annual Meeting, Orlando, FL, 2013.

Gonzales E, Ng G, Pesce A, et al.: Stability of pain-related medications, metabolites, and illicit substances in urine. Clin Chim Acta. 2013; 416: 80-85.

Skopp G, Potsch L: An investigation of the stability of free and glucuronidated 11-nor-9-tetrahydrocannabinol-9-carboxylic acid in authentic urine samples. J Anal Toxicol. 2004; 28: 35-40.

Fuller DC, Anderson WH: A simplified procedure for the determination of free codeine, free morphine, and 6-acetylmorphine in urine. J Anal Toxicol. 1992; 16: 315-318.

Ropp PP, Grimaldi F, Burle J, et al.: Determination of 6-monoacetylmorphine and morphine in plasma, whole blood, and urine using high-performance liquid chromatography with electrochemical detection. J Chromatogr B: Biomed Appl. 1994; 661: 245-253.

Paul BD, Mitchell JM, Mell LD Jr, et al.: Gas chromatography/electron impact mass fragmentometric determination of urinary 6-acetylmorphine, a metabolite of heroin. J Anal Toxicol. 1989; 13: 2-7.

Poochikian GK, Cradock JC: Simple high-performance liquid chromatographic method for the separation of 3,6-diacetylmorphine hydrochloride (heroin) and hydrolysis products. J Chromatogr. 1979; 171: 371-376.

Cook JD, Strauss KA, Caplan YH, et al.: Urine pH: The effects of time and temperature after collection. J Anal Toxicol. 2007; 31: 486-496.

O'Kane MJ, McManus P, McGowan N, et al.: Quality error rates in point-of-care testing. Clin Chem. 2011; 57: 1267-1271.

Anderson M: Guidance for noninstrumented point-of-care testing for all health care workers. Lab Med. 2011; 42: 119-120.

Drummer OH: Drug testing in oral fluid. Clin Biochem Rev. 2006; 27: 147-159.

Heltsley R, DePriest A, Black DL, et al.: Oral fluid drug testing of chronic pain patients. I. Positive prevalence rates of licit and illicit drugs. J Anal Toxicol. 2011; 35: 529-540.

Vanstechelman S, Isalberti C, Van der Linden T, et al.: Analytical evaluation of four on-site oral fluid drug testing devices. J Anal Toxicol. 2012; 36: 136-140.

Blencowe T, Pehrsson A, Lillsunde P, et al.: An analytical evaluation of eight on-site oral fluid drug screening devices using laboratory confirmation results from oral fluid. Forensic Sci Int. 2011; 208: 173-179.

Pehrsson A, Blencowe T, Vimpari K, et al.: An evaluation of on-site oral fluid drug screening devices DrugWipe 5+ and Rapid STAT using oral fluid for confirmation analysis. J Anal Toxicol. 2011; 35: 211-218.

Wille SM, Samyn N, Ramirez-Fernandez MM, et al.: Evaluation of on-site oral fluid screening using Drugwipe-5(+), RapidSTAT and Drug Test 5000 for the detection of drugs of abuse in drivers. Forensic Sci Int. 2010; 198: 1-3.

Pehrsson A, Gunnar T, Engblom C, et al.: Roadside oral fluid testing: Comparison of the results of drugwipe 5 and drugwipe benzodiazepines on-site tests with laboratory confirmation results of oral fluid and whole blood. Forensic Sci Int. 2008; 175: 140-148.

Strano-Rossi S, Castrignano E, Anziollotti L, et al.: Evaluation of four oral fluid devices (DDS®, Drugtest 5000®, Drugwipe 5+®, and RapidSTAT®) for on-site monitoring drugged driving in comparison with UHPLC-MS/MS analysis. Forensic Sci Int. 2012; 221: 70-76.

Quest Diagnostics: Prescription drug misuse in America: A report on marijuana and prescription drugs. Quest Diagnostics Health Trends. 2013.

Jenkins AJ, Goldberger BA (eds.): On-Site Drug Testing. Totowa, NJ: The Humana Press, Inc, 2002.

Landon v Kroll Laboratory Specialists, Inc., 2011 NY Slip Op 08567. Appellate Division of the Supreme Court of New York, Second Department.

Published

01/01/2015

How to Cite

DePriest, PharmD, BCPS, A. Z., D. L. Black, PhD, D-ABFT, and T. A. Robert, PhD, D-ABCC. “Immunoassay in Healthcare Testing Applications”. Journal of Opioid Management, vol. 11, no. 1, Jan. 2015, https://wmpllc.org/ojs/index.php/jom/article/view/158.