Commutability of proficiency testing material containing tobramycin: a study within the framework of the Dutch Calibration 2.000 project.

BACKGROUND: Results from external quality assessment schemes (EQASs) can provide information about accuracy and comparability of different measurement methods, provided that the material used in these schemes behave identical to patient samples among the different methods, a characteristic also known as commutability. The aim of this study was to assess the commutability of different matrices for the material used in an EQAS for tobramycin. METHODS: Proficiency testing material (PTM) and patient samples containing tobramycin were prepared, collected, pooled, and distributed to participating laboratories for analysis. Low, medium, and high tobramycin concentrations in liquid human, liquid bovine and lyophilized bovine serum were tested in this study. The patient serum results of every laboratory were plotted against each of the other laboratories, and the distances of the PTM results to the patient serum regression line were calculated. For comparison, these distances were divided by the average within-laboratory standard deviation (SDwl) of the results reported in the official EQAS for tobramycin, resulting in a relative residual. The commutability decision limit was set at 3 SDwl. RESULTS: With 10 laboratories participating in this study, 45 laboratory couples were formed. For human serum, only one relative residual for high concentrations of tobramycin was found outside the commutability decision limit. For liquid and lyophilized bovine sera, the number of relative residuals outside the decision limit was between 15 and 18 for low, medium, and high tobramycin concentrations. CONCLUSIONS: The PTM used for tobramycin is preferably prepared with human serum.

A Multilaboratory Commutability Evaluation of Proficiency Testing Material for Carbamazepine and Valproic Acid: A Study Within the Framework of the Dutch Calibration 2000 Project.

BACKGROUND: Medical laboratories are required to participate in interlaboratory comparisons of the analyses they perform. The materials used in these comparisons need to be of sufficient quality so that the comparison provides a picture of the performances. One of the main characteristics of the testing material is commutability, which is the ability of a material to yield the same numerical relationships between results of measurements as those relationships obtained when the same procedures are applied to patient samples. The aim of this study was to assess the commutability of 3 different matrices for the preparation of proficiency testing material (PTM) for the analysis of carbamazepine and valproic acid. METHODS: Patient samples and PTM containing various concentrations of carbamazepine and valproic acid were collected, prepared, and shipped to different laboratories for analysis. Reported results for patient samples from each laboratory were plotted against results for patient samples of each of the other laboratories, and the corresponding regression line was calculated. The distance of results from PTM to the regression line is a measure for commutability. The distance is expressed as a multiple of the SDwl (average within-laboratory SD as calculated from external quality assessment scheme results) and referred to as relative residual. A commutability decision limit of 2 SDwl was set. RESULTS: For carbamazepine and valproic acid, a total of 78 and 105 laboratory couples respectively could be formed. The number of relative residuals for liquid human serum outside the commutability decision limit was 1, 4, and 0 for low, medium, and high concentrations of carbamazepine, respectively and 3, 1, and 0 for low, medium, and high concentrations of valproic acid, respectively. In both liquid and lyophilized bovine sera, the number of relative residuals outside the commutability decision limit was between 2 and 15 and between 6 and 21 for carbamazepine and valproic acid, respectively. CONCLUSIONS: Although not all results for PTM with carbamazepine and valproic acid are within the commutability decision limits, a preference for human serum can be seen.

Poor performance of laboratories assaying newly developed antiretroviral agents: results for darunavir, etravirine, and raltegravir from the international quality control program for therapeutic drug monitoring of antiretroviral drugs in human plasma/serum.

BACKGROUND: The International Interlaboratory Quality Control PROGRAM for Therapeutic Drug Monitoring of Antiretroviral Drugs in Human Plasma/Serum was initiated in 1999. We have previously published our experience during the first 10 years of the PROGRAM. Since 2010, 3 newly developed antiretroviral agents have been added to the PROGRAM: darunavir, etravirine, and raltegravir. The objective of this analysis is to describe the performance of participating laboratories measuring these newer agents in 2011-2012. MATERIALS AND METHODS: Each year, laboratories received 2 blind samples of human plasma/serum spiked with a low (<1.0 mg/L), medium (1.0-5.0 mg/L), or high (>5.0 mg/L) concentration of these drugs. Laboratory results were standardized to percentages with reference to the nominal (true) concentration. Any result that deviated more than 20% of the nominal values was defined as inaccurate. RESULTS: The numbers of laboratories that participated by the end of 2012 were 44 for darunavir, 28 for etravirine, and 30 for raltegravir. A total of 357 results were evaluable for analysis. Of these, 64 (17.9%) results were reported with >20% deviation, so "inaccurate" (7.6% too low, 10.4% too high). The proportion of inaccurate results in 2011 was 21.3% for darunavir, 31.0% for etravirine, and 26.3% for raltegravir; in 2012, these figures improved to 8.1%, 23.2%, and 8.3% for darunavir, etravirine, and raltegravir, respectively. Taking darunavir as the reference, performance for etravirine was significantly lower [odds ratio = 0.462, 95% confidence interval: 0.246-0.866, P = 0.016] and performance for raltegravir was not significantly different. Low concentrations were significantly more frequently reported as inaccurate than medium or high concentrations: 28.6% versus 10.6% versus 8.8%, respectively (P < 0.001). Laboratories that used Liquid Chromatography with tandem Mass Spectrometry did not perform better than those using High Performance Liquid Chromatography/Ultrarapid Performance Liquid Chromatography: 41 inaccurate results in 200 samples (20.5%) versus 23 in 157 samples (14.6%, P = 0.154). Multiple logistic regression revealed that the concentration range was the only significant predictor of inaccurate results. The lower range of concentrations performed worse than medium or high concentrations (P < 0.001). CONCLUSIONS: Laboratories continue to have problems with adequately measuring low plasma concentrations of antiretroviral agents. This is particularly a problem for some of the newer antiretroviral agents with plasma concentrations in the <1.0 mg/L range, such as etravirine and raltegravir.

Commutability of proficiency testing material containing amitriptyline and nortriptyline: A study within the framework of the Dutch Calibration 2.000 project.

BACKGROUND: External quality assessment schemes (EQAS) can provide important information regarding accuracy and comparability of different measurement methods if the sample matrices are composed of commutable material. The aim of this study was to assess the commutability of different matrices for the material used in an EQAS for amitriptyline and nortriptyline. METHODS: Proficiency testing material (PTM) and patient samples containing amitriptyline and nortriptyline were prepared, collected, pooled, and distributed to participating laboratories for analysis. Low, medium and high concentrations of both drugs in liquid pooled human, lyophilized human and lyophilized bovine serum were tested in this study. The measurement deviation of the PTM results to the patient serum regression line were normalized by dividing trough the average within-laboratory SD (SDwl) derived from the results reported in the official EQAS, resulting in a relative residual. The commutability decision limit was set at 3 SDwl. RESULTS: With 10 laboratories participating in this study, 45 laboratory couples were formed. All matrix types delivered several relative residuals outside the commutability decision limit. The number and the magnitude of relative residuals for both drugs were lower for liquid human sera as compared to lyophilized human and bovine sera. CONCLUSIONS: The PTM used for amitriptyline and nortriptyline is preferably prepared with human serum, although not all relative residuals are within the commutability decision limit.

The use of amlodipine, but not of P-glycoprotein inhibiting calcium channel blockers is associated with clopidogrel poor-response.

Clopidogrel is a prodrug that has to be converted in vivo to its active metabolite by cytochrome (CYP)P450 iso-enzymes. As calcium channel blockers (CCBs) are inhibitors of CYP3A4, concomitant use of these drugs might play a role in the wide inter-individual variability in the response to clopidogrel. However, some CCBs also have strong inhibitory effects on the drug transporter P-glycoprotein (Pgp), which mediates clopidogrel's intestinal absorption. It was the aim of this study to evaluate the effect of co-administration of Pgp-inhibiting and non-Pgp-inhibiting CCBs on on-clopidogrel platelet reactivity in patients on dual antiplatelet therapy undergoing elective percutaneous coronary intervention (PCI). In a total of 623 consecutive patients undergoing elective PCI treated with clopidogrel and aspirin, platelet reactivity to 5 and 20 muM adenosine diphospate (ADP) and clopidogrel poor-response (defined as > 70% platelet aggregation to 20 muM ADP) were evaluated by light transmittance aggregometry. A total of 222 patients (35.6%) were on CCB treatment, of which 98 used Pgp-inhibiting CCBs (verapamil, nifedipine, diltiazem, barnidipine) and 124 patients used the non-Pgp-inhibiting CCB amlodipine. Adjusted mean ADP-induced on-clopidogrel platelet reactivity was significantly higher in both users of Pgp-inhibiting CCBs and amlodipine as compared to CCB non-users (all p<0.05). However, only the use of amlodipine was significantly associated with a 2.3-fold increased risk of clopidogrel poor-response. This study demonstrates that concomitant use of Pgp-inhibiting CCBs and amlodipine increases on-clopidogrel platelet reactivity. Only amlodipine was associated with clopidogrel poor-response. The drug-drug interaction between clopidogrel and amlodipine might be more clinically relevant as compared to P-glycoprotein-inhibiting CCBs.