“…Another recent study by Ghareeb [ 106 ] revealed that reducing blood contamination in the saliva by rinsing the oral cavity with water before sampling could improve the correlation coefficient between tacrolimus concentrations in oral fluid and whole blood. Another problem has been observed in some antiretroviral and antihypertensive drugs that are detected in very low concentrations in saliva [ 107 , 108 ]. For example, tenofovir is poorly diffused in saliva because it is almost completely ionized under physiological conditions and the ionized form has difficulty passing through the salivary glands [ 107 ].…”
“…Another recent study by Ghareeb [ 106 ] revealed that reducing blood contamination in the saliva by rinsing the oral cavity with water before sampling could improve the correlation coefficient between tacrolimus concentrations in oral fluid and whole blood. Another problem has been observed in some antiretroviral and antihypertensive drugs that are detected in very low concentrations in saliva [ 107 , 108 ]. For example, tenofovir is poorly diffused in saliva because it is almost completely ionized under physiological conditions and the ionized form has difficulty passing through the salivary glands [ 107 ].…”
“…Due to the high sensitivity and specificity, LC-MS/MS has been the main instrument of choice for the quantitative determination of therapeutic drugs in biosamples for this healthcare application. However, the monopoly of the tandem (MS/ MS) system is now being challenged by hyphenated HRMS systems with several studies using this approach to determine drug concentrations in biosamples to assess adherence to prescribed drug therapy [11,19,33,34,44,47,49,52,53,56,62,79].…”
Section: Hyphenated Ms Techniques For Assessing Medication Adherencementioning
confidence: 99%
“…It is only through the increased sophistication and detection capabilities of MS instruments that the microvolume DBS and VAMS sample can provide comparable data to a 1 mL blood sample. This enhanced analytical capability has also spurned the investigation of alternate less invasive biosample matrices including hair and saliva for assessing medication adherence [10,11,58,63,65,66,68,70,73,78,84,86,118,[129][130][131]. The choice of the most appropriate biosample would depend on a number of factors including the ease of sample collection from the patient and knowing if the available biosample size contains sufficient target analyte to be detected.…”
Section: Biological Sample Collectionmentioning
confidence: 99%
“…Historically, saliva has been less used in medication adherence studies, due to various limitations, but the reemergence of this minimally-invasive sampling matrix is probably due to the increased MS instrumental detection capabilities coupled with the potential in saliva to directly measure the therapeutically active free non-protein bound drug and the ease of sampling collection [135,136]. This sampling matrix was recently investigated to assess adherence to antihypertensive drugs where saliva produced comparable results to plasma except for acidic drug compounds [11].…”
Section: Biological Sample Collectionmentioning
confidence: 99%
“…Directly assessing drug, metabolite or biomarker levels in blood and urine samples provides an objective measure but levels may vary due to differences in patient metabolism and pharmacogenetics. Due to the ease of collection and non-invasiveness among other advantages, hair and saliva biosamples have been explored in medication adherence studies [10,11]. For therapeutic drugs there are well-documented pharmacokinetic relationships between the drug dose given and concentration of the drug in the blood stream.…”
Nonadherence to prescribed pharmacotherapy is an understated public health problem globally and is costing many patients their chance to return to good health and healthcare systems billions. Clinicians need an accurate assessment of adherence to medications to aid the clinical decision-making process in the event of poor patient progress and to maximise the patient health outcomes from the drug therapies prescribed. An overview of indirect and direct methods used to measure medication adherence is presented, highlighting the potential for accurate measuring of drugs in biological samples using hyphenated mass spectrometry (MS) techniques to provide healthcare professionals with a reliable evidence base for clinical decision making. In this review we summarise published applications of hyphenated MS techniques for a diverse range of clinical areas demonstrating the rise in the use of such direct methods for assessing medication adherence. Although liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods using plasma, serum and urine samples are the most popular, in recent years increased attention has been given to liquid chromatography high-resolution mass spectrometry (LC-HRMS) methods and alternative biosample matrices including hair, saliva and blood microsamples. The advantages and challenges of using hyphenated MS techniques to address this healthcare problem are also discussed alongside future perspectives.
To study the appropriateness of phlebotomy for digoxin therapeutic drug monitoring (TDM) in outpatients, we conducted a retrospective chart review, a computer search of all previous TDM testing, and a questionnaire of all outpatients (n = 86) who had serum digoxin determinations between April 10 and April 28, 1992 (585 tests). In patients who took digoxin at the same time daily (40 patients, 300 tests), 52% of tests were performed on inappropriate samples drawn within 6 h of the last dose. No patient who took digoxin after 1700 had inappropriate tests. Phlebotomy for serum digoxin determinations before distribution of digoxin is complete is a common problem in outpatients, leading to clinically uninterpretable test results. Postdistribution sampling can be assured by nighttime dosing, and this recommendation has been implemented at our hospital. INDEXING TERMS: blood sampling #{149} pharmacokinetics Digoxin is one of the most widely prescribed drugs for both inpatients and outpatients /1], and digoxin serum concentration is the most commonly ordered therapeutic drug monitoring (TDM) test in the US. Digoxin serum concentrations have been shown to be useful in corroborating the clinical diagnosis of digoxin toxicity as well as correlating with therapeutic effects of digoxin [2, 3]. Digoxin pharmacokinetics are complex hut well characterized (for a review see [4]). For oral dosing of digoxin, rapid absorption occurs in the intestine /4/; reaching distributional equilibrium after a digoxin dose requires at least 8 h, the time at which the semilog plots of plasma and tissue concentrations vs time reach terminal linear and parallel slopes [4, 5]. Samples obtained within 8 h after a digoxin dose can be very misleading as an index of digoxin response /4/.
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