Drug Testing in Oral Fluid.docx
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Drug Testing in Oral Fluid.docx
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DrugTestinginOralFluid
DrugTestinginOralFluid
OlafHDrummer
Abstract
Overthelastdecadetherehavebeenconsiderabledevelopmentsintheuseoforalfluid(saliva)fordrugtesting.Oralfluidcanprovideaquickandnon-invasivespecimenfordrugtesting.However,itscollectionmaybethwartedbylackofavailablefluidduetoarangeofphysiologicalfactors,includingdruguseitself.Foodandtechniquesdesignedtostimulateproductionoforalfluidcanalsoaffecttheconcentrationofdrugs.Currentapplicationsaremainlyfocusedondrugsofabusetestinginemployeesatworkplaceswheredrugusehassafetyimplications,indriversofvehiclesattheroadsideandinothersituationswheredrugimpairmentissuspected.Testinghasincludedalcohol(ethanol)andarangeofclinicaltestsegantibodiestoHIV,therapeuticdrugsandsteroids.Itsmainapplicationhasbeenfortestingfordrugsofabusesuchastheamphetamines,cocaineandmetabolites,opioidssuchasmorphine,methadoneandheroin,andforcannabis.Oralfluidconcentrationsofbasicdrugssuchastheamphetamines,cocaineandsomeopioidsaresimilarorhigherthanthoseinplasma.Tetrahydrocannabinol(THC),themajorspeciespresentfromcannabisuse,displayssimilarconcentrationsinoralfluidcomparedtobloodintheeliminationphase.However,thereissignificantlocalabsorptionofthedrugintheoralcavitywhichincreasestheconcentrationsforaperiodafteruseofdrug.Depoteffectsoccurforotherdrugsintroducedintothebodythatallowlocalabsorption,suchassmokingoftobacco(nicotine),cocaine,amphetamines,oruseofsub-lingualbuprenorphine.Screeningtechniquesareusuallyanadaptationofthoseusedinotherspecimens,withanemphasisontheparentdrugsincethisisusuallythedominantspeciespresentinoralfluid.Confirmatorytechniquesarelargelybasedonmassspectrometry(MS)withanemphasisonLiquidChromatography-MassSpectrometry(LC-MS),duetolowsamplevolumesandthelowdetectionlimitsrequired.Drugtestingoutsidelaboratoryenvironmentshasbecomewidespreadandprovidespresumptiveresultswithinminutesofcollectionofspecimens.Thisreviewfocusesonthedevelopments,particularlyoverthelast10years,andoutlinestherolesandapplicationsoftestingfordrugsinoralfluid,describesthedifficultiesassociatedwiththisformoftestingandillustratesapplicationsoforalfluidtestingforspecificdrugs.
Introduction
Drugtestinghasundergonemajoradvances,particularlyoverthelast10years.Theuseofalternativespecimenstobloodorurineforestablishingexposuretodrugshasbecomeasignificantdirectioninclinicalandforensictoxicology.1Thesealternativespecimensincludehair,sweatandoralfluid.Oralfluidhasbeenseenasanon-invasivealternativetobloodbutalsoasanalternativetourinewhensubstitutionoradulterationissuspected.Whiletheseattributesarereal,oralfluidcannotbeseenasasubstituteforbloodorurinedrugtesting.Eachspecimenhasitsowndistinctadvantagesanddisadvantages.
TheintroductionofLC-MSasaroutinelaboratorytechniquehasenabledthebenefitsofHighPerformanceLiquidChromatography(HPLC)separationtechniquestobelinkedtothehighsensitivityandspecificityofMS.2–4Thishasassistedinthedevelopmentofdrugtestinginoralfluidduetotherelativelysmallsamplevolumesthatareusuallycollected.Thelastdecadehasalsoseenasignificantdevelopmentintheunderstandingofthetargetdrugsandtheirpharmacokineticsinoralfluid.Thishasappliedparticularlytotheabuseddrugsandwhatconcentrationsneedtobetargeted,andalsohowtheseconcentrationsmayormaynotrelatetobloodconcentrationsandthelikelydrugeffectsontheindividual.Inaddition,theuseofinitialscreeningcartridgesordevicesprovidinganelectronicreadouthasdevelopedandisnowwidelyused.Inparticular,kitsarenowdesignedforon-sitedrugdetectionwithouttheneedforsophisticatedlaboratoryscreeningequipment.Theseareabletoprovideapreliminarydrugresultwithinminutes.
Anumberofreviewsandmajorpaperscurrentlyexistforvariousaspectsofdrugsanddrugtestinginoralfluid.Theseincludeitsuseasadiagnostictool,5workplaceapplications,6applicationsindrugsindriving,7legalissuesassociatedwithdrugtestinginoralfluid,8anddetectiontimesandpharmacokineticsofselecteddrugs.9,10
Thisreviewoutlinestherolesandapplicationsoftestingfordrugsinoralfluid,describestherelativeadvantagesanddisadvantagesofthisformoftestingandillustratesapplicationsoforalfluidtestingforspecificdrugs.
ScopeofReview
Thispaperreviewsthedevelopmentsandapplicationsofdrugtestinginoralfluidparticularlyoverthelast10years.Publishedpeer-reviewedliteratureandotherselectedreferencesintheEnglishlanguageinhumansassourcedbyMedlineandScienceDirect(since1995)arereviewedforclinicalandforensicapplicationsofdrugtestinginoralfluid.Publicationsbeforethistimeareincludedifpivotalorlaterpaperswerenotavailable.Thetermoralfluidreferstosalivaandothersecretionsintheoralcavity.Thefocusisontestingfordrugsofabusesuchastheamphetamines,benzodiazepines,cannabis,cocaineandopioids,butotherapplicationswillbediscussedinthecontextofabuseddrugs.
SourceofOralFluid
Oralfluid(saliva)isexcretedprimarilybythreeglands:
theparotid,submaxillaryandsublingualandbyothersmallerglands.Oralfluidhaslowproteincontent(0.3%)andcanvaryinflowratefromzerotoseveralmLperminutedependingoninfluencesfromvariousfactors,includingemotionalstateandhunger.Drymouthsyndromeisrelativelycommonandcanbecausedbytheanxietyofthecollectionprocedure,orevenbylackofproperhydrationoftheindividual.Drymouthsrequiremuchlongercollectiontimes;oftenseveralminutestocollect1mL.Onsomeoccasionsthismayforcethecollectionofanalternativespecimenifcollectionistooslow,ieblood(unpublisheddata).ApsandMartensprovideanexcellentreviewofphysiologicalandpharmacologicalissuesinvolvedintheproductionoforalfluid.11
CollectionTechniquesandAdulterants
Expectoration(orspitting)providesneatoralfluid,butthisisrelativelyviscousandcanbedifficulttoworkwithinthelaboratory.Itmayalsobecontaminatedwithfoodandotherdebrisfromthemouthandwillthereforerequirecentrifugation.Moreoftenthannot,thevolumewillbelessthan1mLrequiringtheuseofsensitivedetectiontechniques.Someofthecommercialcollectorsavailableusesomeformofproprietarydiluenttomixwiththecollectedoralfluid(Table1).Inthissituation,typicallytheabsorbentpad/foamthatisusedtocollecttheoralfluidisaddedtoadiluent.Followingmixing,thesolutionisusedfordruganalysis.Otherdevicesinvolvesqueezingabsorbedoralfluidfromapadorfoamontothedrug-detectiondevice.Thecollectiontimeistypicallyonetothreeminutes,howeverthiscanvaryasdiscussedearlier.Anumberofthedeviceshavesomeformofindicatortoshowthatsufficientoralfluidhasbeencollected.
Table1SelectionofCollectionDevicesReportedinLiterature.
NameofCollector
MethodofOperation
Reference
DrugWipe®
Swipeonly(tongueorskin)
62, 66, 67, 93, 94
Cozart®collector
Absorbentfoampadplusdiluent
75, 76, 93, 95, 96
DrägerDrugTest®
Absorbentfoampadwithdiluent
97
Intercept®
Absorbentfoampadwithdiluent
77, 83, 98–100
OralScreen®
Absorbentfoampadonly,dropsappliedtodevice
101
OralLab®
Absorbentfoampad,collectorsqueezedtoapplyoralfluidintotestcartridge
93
OraLine®
Directapplicationtooralcavity,oruseofothercollectors
102
OraTect®
Absorbentdirectlyconnectedtodevice
16, 94
Quantisal™
Absorbentfoampadplusdiluent
21
SalivaScreen®
Absorbentfoampad,dropsappliedtodevice
93
Salivette®
Cottonwoolswabwhichisthenfilteredandcentrifuged
12, 19, 66, 103
Toxiquick®
Absorbentbud,oralfluidsqueezedintosyringeandappliedtodevice
104
TheDrugWipe®onlyinvolvesswipingacollectionpadonthetongueorskin,aprocessthattakesonlyseconds(Table1).However,thereisnooralfluidforanyconfirmatoryassayiftheresultispositive.
Oralfluidproductionisstimulatedbyuseofagentssuchascitricacidcandy,chewinggumorotheragents.ThiswillinevitablychangethepHandconcentrationofdrugintheoralfluid.Thishasbeenshowntolowerconcentrationsofcodeinebyabouttwo-tosix-fold,12,13two-tofour-foldformethamphetamine,14andaboutfive-foldforcocaine.15Itislikelythatsimilarchangeswilloccurforotherdrugs.
Anumberofdrugsareknowntoaffectthesecretionoforalfluid.11Mostcommonlytheseareamphetamines,includingthedesignerformssuchasecstasy(MDMA),andcannabis.Otherdrugsincludethesedatingantihistamines,antipsychoticdrugs,anticholinergicdrugsandanumberofantidepressants.Therearelesscommonlyuseddrugsthatincreaseflowandtheseincludeclonidine,pilocarpineandbeta-2stimulants(salbutamol,terbutalineetc).
Consequently,thereissignificantintra-andinter-subjectvariationinrelationtodrugconcentrationsdependingonthetechniqueused,thephysiologyofthepersonandtheinfluenceoffactorsaffectingdrugconcentrationinoralfluid.
Sincethecollectionoforalfluidspecimencanbeviewedbyasecondpersonwithoutinfringingprivacyitdoesnotsufferfromthesameissuesregardingpossibleadulterationorsubstitutionasforurine.13Whilethiscanbeadistinctadvantage,itmustberecognisedthatmethodscanbeemployedtopotentiallyaffectthecollectionoforalfluidortheconcentrationofdru
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