Detection and Quantitation of Pain Medications in Oral Fluid Specimens
A method for the detection and quantitation of pain medication in oral fluid specimens is provided. First, a Solid Phase Extraction (“SPE”) process is used to isolate cocaine and its metabolite, amphetamines and/or butalbital from human oral fluid samples. Alternatively, Liquid-Liquid Extraction (“LLE”) is used to isolate methadone and its metabolite, fentanyl and norfentanyl, buprenorphine and norbuprenorphine, propoxyphene and norpropoxyphene, carisoprodol, meprobamate, a series of benzodiazepines, tramadol and its metabolites, the analgesic opioids, and tetrahydrocannabinol (“THC”) and its carboxylated metabolite (“THC-C”). Finally, following isolation of these drugs and their metabolites, they are separated respectively using a high performance liquid chromatographic column and a novel combination chromatographic solvents and gradients. All analytes are detected and quantified using a tandem mass spectrometry (“MS/MS”) precursor to produce ion transitions.
1 . A method of detecting and quantifying the presence of a drug relevant to pain management therapies, said method comprising:
obtaining an oral fluid specimen from a patient, said specimen comprising native constituents and one or more compounds of interest;
detecting and isolating said compounds of interest from said native constituents by means of solid phase extraction;
separating said compounds of interest using a liquid chromatographic column and one or more chromatographic solvents; and
identifying and quantifying said compounds of interest using a tandem mass spectrometry precursor to produce measurable ion transitions.
2 . The method of claim 1 , wherein separating said compounds of interest further comprises the use of one or more chromatographic gradients.
3 . The method of claim 1 , wherein said compounds of interest comprise at least one member of the group consisting of cocaine or a metabolite thereof, an amphetamine, and butalbital.
4 . The method of claim 1 , further comprising the steps of:
using a second portion of the oral fluid specimen from the patient, said second portion comprising expected constituents and detectable compounds;
detecting and then isolating said detectable compounds from said expected constituents by means of liquid-liquid extraction;
separating said detectable compounds using said liquid chromatographic column and a second combination of chromatographic solvents, and
identifying and quantifying said detectable compounds using a tandem mass spectrometry precursor to produce measurable ion transitions.
5 . The method of claim 3 , wherein said metabolite is benzoylecogonine.
6 . The method of claim 4 , wherein separating said detectable compounds further comprises a second combination of chromatographic gradients.
7 . The method of claim 4 , wherein said detectable compounds comprise at least one member selected from the group consisting of: methadone or a methadone metabolite, fentanyl, norfentanyl, buprenorphine, norbuprenorphine, propoxyphene, norpropoxyphene, carisoprodol, meprobamate, a series of benzodiazepines, tramadol or a tramadol metabolite, and analgesic opioids.
8 . The method of claim 4 , wherein said detectable compounds comprise at least one of tetrahydrocannabinol and a tetrahydrocannabinol metabolite.
9 . The method of claim 7 , wherein said methadone metabolite further comprises EDDP.
10 . The method of claim 7 , wherein said series of benzodiazepines further comprises one or more of alprazolam, diazepam, nordiazepam, oxazepam, temazepam, flurazepam, clonazepam and lorazepam.
11 . The method of claim 7 , wherein said tramadol metabolites further comprise one or more of o-desmethyltramadol and n-desmethyltramadol.
12 . The method of claim 7 , wherein said analgesic opioid further comprises one or more of codeine, norcodeine, dihydrocodeine, morphine, hydromorphone, oxymorphone, hydrocodone, norhydrocodone, oxycodone and noroxycodone.
13 . The method of claim 8 , wherein said tetrahydrocannabinol metabolite further comprises THC-C.
14 . A method of detecting and quantifying the presence of a drug relevant to a pain management therapy, said method comprising:
obtaining an oral fluid specimen from the patient, said specimen comprising expected constituents and detectable compounds;
detecting and isolating said detectable compounds from said expected constituents by means of liquid-liquid extraction;
separating said detectable compounds using a liquid chromatographic column and a combination of chromatographic solvents; and
identifying and quantifying said detectable compounds using a tandem mass spectrometry precursor to produce measurable ion transitions.
15 . The method of claim 14 , wherein separating said detectable compounds further comprises using a combination of chromatographic gradients.
16 . The method of claim 14 , wherein said detectable compounds comprise at least one member selected from the group consisting of: methadone or a methadone metabolite, fentanyl, norfentanyl, buprenorphine, norbuprenorphine, propoxyphene, norpropoxyphene, carisoprodol, meprobamate, a series of benzodiazepines, tramadol or a tramadol metabolite, analgesic opioids, and tetrahydrocannabinol or a tetrahydrocannabinol metabolite.
17 . The method of claim 16 , wherein said methadone metabolite comprises EDDP.
18 . The method of claim 16 , wherein said series of benzodiazepines further comprises one or more of alprazolam, diazepam, nordiazepam, oxazepam, temazepam, flurazepam, clonazepam, and lorazepam.
19 . The method of claim 16 , wherein said tramadol metabolites further comprises one or more of o-desmethyltramadol and n-desmethyltramadol.
20 . The method of claim 16 , wherein said analgesic opioids further comprises one or more of codeine, norcodeine, dihydrocodeine, morphine, hydromorphone, oxymorphone, hydrocodone, norhydrocodone, oxycodone and noroxycodone.
21 . The method of claim 16 , wherein said tetrahydrocannabinol metabolite further comprises THC-C.