Ensuring quality in 17OHP mass spectrometry measurement: an international study assessing isomeric steroid interference.

OBJECTIVES: Interference from isomeric steroids is a potential cause of disparity between mass spectrometry-based 17-hydroxyprogesterone (17OHP) results. We aimed to assess the proficiency of mass spectrometry laboratories to report 17OHP in the presence of known isomeric steroids. METHODS: A series of five samples were prepared using a previously demonstrated commutable approach. These samples included a control (spiked to 15.0 nmol/L 17OHP) and four challenge samples further enriched with equimolar concentrations of 17OHP isomers (11α-hydroxyprogesterone, 11ß-hydroxyprogesterone, 16α-hydroxyprogesterone or 21-hydroxyprogesterone). These samples were distributed to 38 participating laboratories that reported serum 17OHP results using mass spectrometry in two external quality assurance programs. The result for each challenge sample was compared to the control sample submitted by each participant. RESULTS: Twenty-six laboratories (68 % of distribution) across three continents returned results. Twenty-five laboratories used liquid chromatography-tandem mass spectrometry (LC-MS/MS), and one used gas chromatography-tandem mass spectrometry to measure 17OHP. The all-method median of the control sample was 14.3 nmol/L, ranging from 12.4 to 17.6 nmol/L. One laboratory had results that approached the lower limit of tolerance (minus 17.7 % of the control sample), suggesting the isomeric steroid caused an irregular result. CONCLUSIONS: Most participating laboratories demonstrated their ability to reliably measure 17OHP in the presence of the four clinically relevant isomeric steroids. The performance of the 12 (32 %) laboratories that did not engage in this activity remains unclear. We recommend that all laboratories offering LC-MS/MS analysis of 17OHP in serum, plasma, or dried bloodspots determine that the isomeric steroids are appropriately separated.

Lack of Effects of Renin-Angiotensin-Aldosterone System Activity and Beta-Adrenoceptor Pathway Polymorphisms on the Response to Bisoprolol in Hypertension.

Purpose: This study examined the effects of plasma renin activity (PRA), angiotensin II (Ang II) and aldosterone (PAC) concentrations as well as common polymorphisms in the ß1-Adrenoceptor gene (ADRB1) and the G-protein α-Subunit (Gαs) protein gene the G protein α-Subunit 1 gene (GNAS) on the blood pressure (BP) and heart rate (HR) response to bisoprolol in Chinese patients with hypertension. Methods: Patients with sitting clinic systolic BP (SBP) 140-169 mmHg and/or diastolic BP (DBP) 90-109 mmHg after placebo run-in were treated with open-label bisoprolol 2.5 mg daily for 6 weeks. Patients diagnosed as having primary aldosteronism or renal artery stenosis were excluded. PRA, Ang II and PAC concentrations were measured after the placebo run-in and after 6 weeks of treatment. The Ser49Gly and Arg389Gly polymorphisms in ADRB1 and the c.393C > T polymorphism in GNAS were genotyped by the TaqMan® assay. Results: In 99 patients who completed the study, baseline PAC levels were significantly associated with baseline DBP and plasma potassium on univariate but not on multivariate linear regression analysis. PRA, Ang II, and PAC concentrations at baseline were not associated with changes in BP with bisoprolol treatment, but the values were all significantly reduced (PRA -0.141 ± 0.595 ng/mL/h, Ang II -2.390 ± 5.171 pmol/L and aldosterone -51.86 ± 119.1 pg/mL; all P < 0.05) following 6 weeks of bisoprolol treatment. There were no significant differences in BP or HR responses in patients with baseline PRA above or below the PRA cut-point of 0.65 ng/mL/h or the median value of 0.9 ng/ml/hour. There were no significant associations of the ADRB1 and GNAS polymorphisms with the clinic and ambulatory BP and HR responses to bisoprolol. Conclusion: Baseline PRA, PAC and Ang II concentrations showed no significant association with the BP response to bisoprolol treatment, but all these parameters were reduced after 6 weeks of treatment with bisoprolol. The two common polymorphisms in ADRB1 and the c.393C > T polymorphism in GNAS had no significant association with the BP and HR response to bisoprolol in these patients.

Performance of a point-of-care device for oral fluid ketamine evaluated by a liquid chromatography-tandem mass spectrometry method.

The performance of a point-of-care device, the OratectXP Oral Fluid Drug Screen Device for Ketamine, was evaluated. The cutoff specification for the device was for ketamine at 15 ng/mL. A total of 72 authentic oral fluid samples were collected from volunteers at two local rehabilitation centers for clients with addiction to drugs of abuse. These samples were tested with the device for visual detection of ketamine and also measured by a liquid chromatography isotope-dilution tandem mass spectrometry method for ketamine, norketamine and dehydronorketamine concentrations. Sensitivity of the device was 87.5% when tested by 24 authentic oral fluid samples with ketamine concentrations ≥ 15 ng/mL. False positive rate of the device was 4.5%. Specificity of the device was 97.9% when tested by 48 authentic oral fluid samples with ketamine concentrations < 15 ng/mL. False negative rate of the device was 6%. The overall efficiency of the device was 94%. According to the desirable acceptance criteria proposed by the "Driving Under the Influence of Drugs, Alcohol, and Medicines" project, the performance of the OratectXP was satisfactory and achieved the minimum standard for testing drivers under the influence of drugs. Furthermore, we propose the confirmation cutoff level for oral fluid ketamine to be at 25 ng/mL.