Stability of pain-related medications, metabolites, and illicit substances in urine (original) (raw)
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Analytical Considerations When Monitoring Pain Medications by LC-MS/MS
Journal of Analytical & Bioanalytical Techniques, 2014
Background: Laboratory urine drug testing of patients on chronic opioid therapy requires providing a large test menu of medications commonly prescribed for this population as well as metabolites and illicit substances. It has been shown that liquid chromatography-tandem mass spectrometry (LC-MS/MS) is the preferred method to analyze urine specimens for these substances. Purpose of the study: To describe the challenges and some of the techniques to validate the analytical procedures used to identify and quantify these medications and substances. Methods: Using data obtained from testing over one million specimens, the authors developed a proposed test menu. Potential isobaric interferences were established by using literature references. A list of potentially interfering medications was obtained by using the proposed test menu and the most commonly prescribed medications. Finally, criteria were designed to detect possible carryover. Results: The LC-MS/MS instrumentation eliminated all potential interferences and provided quantitative data over the test range needed to monitor these patients. Carryover could be eliminated by setting the carryover thresholds for each analyte. Conclusions: Reference laboratories utilizing LC-MS/MS technology to conduct urine drug testing for pain clinicians should employ specific techniques described in this study to develop an optimal test menu and validate procedures that include isolating retention times for isobaric compounds, identifying interfering substances including impurities in medicinal and illicit substance preparations, monitoring ion suppression, and avoiding carryover.
Urine Drug Testing of Chronic Pain Patients: Licit and Illicit Drug Patterns
Journal of Analytical Toxicology, 2008
Chronic pain patients are frequently maintained on one or more powerful opioid medications in combination with other psychoactive medications. Urine tests provide objective information regarding patient compliance status. Little information is available on testing this unique population. The goal of this study was to characterize drug disposition patterns in urine specimens collected from a large population of pain patients. Confirmation data for 10,922 positive specimens were collated into 11 drug Classes. The number of drug/metabolites tested (#) and number of confirmed positive specimens were as follows: amphetamines (7), 160; barbiturates (5), 308; benzodiazepines (6), 2397; cannabinoids (1), 967; carisoprodol (2), 611; cocaine (1), 310; fentanyl (1), 458; meperidine (2), 58; methadone (2), 1209; opiates (7), 8996; and propoxyphene (2), 385. Subdivision into 19 distinct drug Groups allowed characterization of drug use patterns. Of the 10,922 positive specimens, 15,859 results were reported as positive in various drug Classes, and 27,197 drug/metabolites were measured by gas chromatography-mass spectrometry. The frequency of illicit drug use (cannabis, cocaine, ecstasy) was 10.8%. Being the first study of this type, these data present a large array of information on licit and illicit drug use, drug detection frequencies, drug/metabolite patterns, and multi-drug use combinations in pain patients.
Pain physician
Immunoassay screening is used by pain physicians to determine compliance with controlled substances. Because clinical use of pain medications is different from illicit drug use, there is a need to evaluate the level of diagnostic accuracy of this procedure for the pain patient. To compare the results of automated screening by immunoassay with analysis by Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) in identifying pain patients using illicit drugs and pain patients excreting low concentrations of their prescribed medications. A diagnostic accuracy study. Urine samples from 4,200 pain patients were tested by immunoassay and LC-MS/MS for the following drugs and metabolites: Amphetamine, Methamphetamine, Alpha-hydroxyalprazolam, Lorazepam, Nordiazepam, Oxazepam, Temazepam, Cannabinoids, Cocaine, Methadone, Methadone Metabolite, Codeine, Hydrocodone, Hydromorphone, Morphine, Propoxyphene, and Norpropoxyphene. In a number of patients negative immunoassay findings were superse...
The Journal of Applied Laboratory Medicine, 2017
The AACC Academy, formerly the National Academy of Clinical Biochemistry, has developed a laboratory medicine practice guideline (LMPG) 10 for using laboratory tests to monitor drug therapy in pain management patients. The purpose of this guideline was to compile evidence-based recommendations for the use of laboratory and point-ofcare (POC) urine drug tests for relevant over-thecounter medications, prescribed and nonprescribed drugs, and illicit substances in pain management patients. The exact process of preparing and publishing the LMPG is shown in Table 1. Briefly, a multidisciplinary LMPG committee was established to include clinical laboratory professionals, clinicians practicing in pain management, and other relevant stakeholders, healthcare professionals, and clinical experts. The experts on the committee are listed in the guideline and represented the AACC Academy (L.J. Langman, P.J. Jannetto); Clinical and Laboratory Standards Institute, which is jointly preparing an expert opinion guideline on laboratory testing for pain management (C.A. Hammett-Stabler, L.J. Langman, G.A. McMillin); College of American Pathologists (S.E. Melanson); Evidence-Based Laboratory Medicine Committee (W.A. Clark); clinical laboratories performing pain management testing (L.
Pain physician
The challenge for physicians in treating chronic pain with opioids is to eliminate or significantly curtail abuse of controlled prescription drugs while assuring proper treatment when indicated. Urine drug testing (UDT) has been shown to be a useful approach in identifying patterns of compliance, misuse, and abuse. However, significant controversy surrounds the diagnostic accuracy of UDT performed in the office (immunoassay) and the requirement for laboratory confirmation with liquid chromatography tandem mass spectrometry (LC/MS/MS). A diagnostic accuracy study of urine drug testing. The study was performed in an interventional pain management practice, a tertiary referral center, in the United States. The objective of this study was to compare the results of UDT of immunoassay in-office testing (index test) to LC/MS/MS (reference test). One-thousand participants were recruited from an interventional pain management program. Urine sample was collected from all the consecutive patie...
Pain medicine (Malden, Mass.), 2017
To develop consensus recommendations on urine drug monitoring (UDM) in patients with chronic pain who are prescribed opioids. An interdisciplinary group of clinicians with expertise in pain, substance use disorders, and primary care conducted virtual meetings to review relevant literature and existing guidelines and share their clinical experience in UDM before reaching consensus recommendations. Definitive (e.g., chromatography-based) testing is recommended as most clinically appropriate for UDM because of its accuracy; however, institutional or payer policies may require initial use of presumptive testing (i.e., immunoassay). The rational choice of substances to analyze for UDM involves considerations that are specific to each patient and related to illicit drug availability. Appropriate opioid risk stratification is based on patient history (especially psychiatric conditions or history of opioid or substance use disorder), prescription drug monitoring program data, results from v...
Toxicity and Drug Testing, 2012
Pain is a complex disease. The complexities and co-morbidities of this disease include depression, anxiety, addiction, and other psychological diagnoses that lead to difficulties in management and aberrant behavior such as not taking medications as prescribed, taking additional medications, or illicit drugs. In the effort to provide the highest standard of care for their patients, pain physicians are required to continually assess patients for addiction and, if necessary, refer them to addictionologists for additional treatment (Chou et al., 2009). 1.1 Chronic opioid therapy In this chapter we will refer to pain patients as those persons being treated with chronic opioid therapy for non-cancer-related pain. It is this patient population that has been associated with opiate abuse and diversion, and therefore monitoring these patients for drug use in a manner analogous to therapeutic drug monitoring is necessary. One of the most frequent complaints by patients seeing pain physicians is back pain, which is often associated with failed back surgery (Manchikanti et al., 2004; Michna et al., 2007). Currently opiate medications are one of the treatments of choice used by physicians to provide pain relief. These medications can induce euphoria as well as pain relief; because of this, opiates are frequently abused by this population, as well as the general population (National Survey on Drug Use and Health: Detailed Tables-Prevalence Estimates, Standard Errors, P Values, and Sample Sizes, 1995-2006; Webster & Dove, 2007). Additionally, these medications are associated with physical as well as psychological dependence and can pose addiction risks (Webster & Dove, 2007). 1.2 Pain treatment One of the treatments of choice for chronic pain involves strong medications such as opioids, as well as additional or adjuvant medications (Chou et al., 2009; Trescot et al., 2006). Side effects of opioids include sedation, dizziness, nausea, vomiting, and constipation. Living day to day with any or all of these symptoms is challenging at the least and is compounded by the underlying pain these patients suffer from. Naturally, patients often www.intechopen.com Toxicity and Drug Testing 26 attempt to minimize the side effects by taking less of the medication when side effects are particularly debilitating or unpleasant. "Chronic pain patients often adjust their dose of prescribed medication in response to changing levels of activity with no malicious or maladaptive intent. Although they may state that their pattern of use of medications is stable, this is often a statement made ''on average'' rather than a precise pattern of use. This is particularly evident with short-acting medications used in the treatment of breakthrough pain." (Gourlay & Heit, 2010b) UDT is used to give confidence to both the physician and the patient that the patient is following the medication regimen and is therefore getting the most benefit from their treatment. In addition, the side effects of these medications often result in their misuse, underuse, and/or mixing of medications that are not prescribed (Manchikanti et al., 2004). This can also result in the social problems of abuse, misuse, or diversion of these medications. These factors require of pain physicians that they be particularly attentive to their prescribing practices. Adding to the complexity of managing pain patients is the fact that these medications are controlled substances and cannot be purchased over the counter, and so have high street value (Katz et al., 2003; National Prescription Drug Threat Assesment, 2009). This in turn requires of the physician that he or she determine whether patients under their care are compliant with their medication regime, binging on their medications, or diverting them for financial gain (Manchikanti et al., 2005, 2006a, 2006b). 1.3 Complications of pain treatment Further compounding the situation, alcohol use is of major concern to the physician because alcohol-drug interactions can cause morbidity (Harmful Interactions: Mixing Alcohol with Medicines, 2007). Although physicians prohibit patient alcohol use during treatment with opiates or benzodiazepines, verbal contracts are commonly broken and therefore alcohol use must be monitored with (UDT) to manage the high risk of alcohol-drug reactions and mortality (Chou et al., 2009; Trescot et al., 2006). In addition, for reasons involving inadequate pain control, sleep deprivation, and psychological pathology, this patient population commonly takes other medications not prescribed by treating physicians as well as illicit drugs (Manchikanti et al., 2005, 2006a, 2006b). To respond to these potential problems, physicians traditionally relied upon behavioral assessment and pill counts to aid them in making treatment decisions. UDT has augmented these tools by providing physicians with objective, scientifically measurable outcomes to help them make decisions
American journal of clinical pathology, 2015
The major objective of this research was to propose a simplified approach for the evaluation of medication adherence in chronic pain management patients, using liquid chromatography time-of-flight (TOF) mass spectrometry, performed in parallel with select homogeneous enzyme immunoassays (HEIAs). We called it a "hybrid" approach to urine drug testing. The hybrid approach was defined based on anticipated positivity rates, availability of commercial reagents for HEIAs, and assay performance, particularly analytical sensitivity and specificity for drug(s) of interest. Subsequent to implementation of the hybrid approach, time to result was compared with that observed with other urine drug testing approaches. Opioids, benzodiazepines, zolpidem, amphetamine-like stimulants, and methylphenidate metabolite were detected by TOF mass spectrometry to maximize specificity and sensitivity of these 37 drug analytes. Barbiturates, cannabinoid metabolite, carisoprodol, cocaine metabolite, ...
Journal of Analytical Toxicology, 2010
This study of 20,089 urine specimens from chronic pain patients provided a unique opportunity to evaluate the prevalence of prescription opiates and metabolites, assess the usefulness of inclusion of normetabolites in the test panel, and compare opiate and oxycodone screening results to liquid chromatography with tandem mass spectrometry (LC-MS-MS) results. All specimens were screened by an opiate [enzyme-linked immunosorbent assay (ELISA), 100 ng/mL] and oxycodone assay [ELISA, 100 ng/mL or enzyme immunoassay (EIA), 50 ng/mL] and simultaneously tested by LC-MS-MS [limit of quantitation (LOQ) = 50 ng/mL] for 10 opiate analytes (codeine, norcodeine, morphine, hydrocodone, dihydrocodeine, norhydrocodone, hydromorphone, oxycodone, noroxycodone, and oxymorphone). Approximately two-thirds of the specimens were positive for one or more opiate analytes. The number of analytes detected in each specimen varied from 1 to 8 with 3 (34.8%) being most prevalent. Hydrocodone and oxycodone (in combination with metabolites) were most prevalent followed by morphine. Norcodeine was only infrequently detected whereas the prevalence of norhydrocodone and noroxycodone was approximately equal to the prevalence of the parent drug. A substantial number of specimens were identified that contained norhydrocodone (n = 943) or noroxycodone (n = 702) but not the parent drug, thereby establishing their interpretative value as biomarkers of parent drug use. Comparison of the two oxycodone screening assays revealed that the oxycodone ELISA had broader cross-reactivity with opiate analytes, and the oxycodone EIA was more specific for oxycodone. Specimens containing only norhydrocodone were best detected with the opiate ELISA whereas noroxycodone (only) specimens were best detected by the oxycodone EIA.
Clinica Chimica Acta, 2019
Background: Many clinical toxicology laboratories receive urine specimens in urine cups that contain point of care (POC) drug testing strips. We conducted this study to evaluate the effect on the stability of commonly measured drugs in the clinical toxicology laboratory when urine is exposed to POC urine drug testing cups. Methods: Drug free urine was spiked with 85 drugs that were measured by a validated liquid chromatography mass spectrometry (LCMS) method after exposure to POC urine drug testing cups at ambient and 2-6°C temperatures. Alterations ≥20% were defined as significant changes in the drugs concentration. Results: Concentrations of amitriptyline, cyclobenzaprine, fentanyl, fluoxetine, flunitrazepam, nortriptyline, paroxetine, and sertraline were significantly reduced when urine specimens were stored inside POC urine drug testing cups for 24 h at ambient temperature. Storage of urine in urine chemistry dipsticks reduced the concentration of several drugs. When spiked urine was exposed to an increasing number of POC urine drug testing strips, the concentrations of some drugs were reduced in a dose-dependent manner. The drugs that were absorbed by POC urine drug testing strips were partially back extracted from the strips. Conclusion: Exposure of urine specimens to POC urine drug testing strips reduces the concentration of several drugs measured by LCMS method.