ABSTRACT
Objective:To explore the clinical utility of liquid chromatography tandem mass spectrometry forprimary aldosteronism screening.Methods:From January to October 2019, 413 inpatients diagnosed hypertension from Fuwai Hospital of Chinese Academy of Medical Sciences were enrolled, including 60 Primary aldosteronism(PA)patients and 353 primary hypertension patients. The plasma aldosterone concentration (PAC) and renin concentration (DRC) were measured after 2 h of standing. The 24 h urine samples were collected for measurement of aldosterone using LC-MS/MS. The performance of urine aldosterone and urine aldosterone/renin ratio (UADRR) in PA screening was evaluated by ROC, and compared with PAC/DRC ratio (ADRR). Meanwhile, the efficiency of urine aldosterone in elderly patients or patients with low blood potassium or 24 h urine sodium over 200 mmol was investigated.Results:Area under the curve (AUC)of urine aldosterone was 0.725 (95 %CI 0.679-0.767), and the best cut-off was 7.13 μg/24 h, which was lower than AUC of ADRR (0.958, 95 %CI 0.934-0.975). The AUC of UADRR was 0.947 (95 %CI 0.920-0.966), the best cut-off was 1.11 (μg/24 h)/(μIU/ml), the sensitivity and specificity were 91.7% and 89.0%, respectively. There is no significant differences found with ADRR. In patients with 24 h urine sodium over 200 mmol, AUC of aldosterone was 0.834 (95 %CI 0.730-0.910) and the best cut-off was 9.31 μg/24 h. The sensitivity and specificity were 90.9% and 68.7%, respectively. For the elderly patients over 60 years old, the AUC of urinary aldosterone was 0.860 (95 %CI 0.770-0.925), and the best cut-off was 6.91 μg/24 h. The sensitivity and specificity were 84.6% and 81.3%, respectively. When admission blood potassium was less than 3.50 mmol/L, AUC of urinary aldosterone was 0.822 (95 %CI 0.684-0.917), and the best cut-off was 10.63 μg/24 h. The sensitivity and specificity were 85.7% and 66.7%, respectively. Conclusion:The detection of aldosterone in urine by LC-MS/MS can provide clinical information for PA screening, and the screening performance is better in patients with 24-hour urine sodium over 200 mmol, elderly patients or patients with low blood potassium. If combined with renin, screening efficiency was the same as that in ADRR.
ABSTRACT
Objective To develop and validate a LC-MS/MS method for determination of rhoifolin in rat plasma and investi?gate its pharmacokinetic properties after intravenous administration to rats. Methods The analyte was isolated from rat plasma by liq?uid-liquid extraction with ethyl acetate. Separation was performed on a Phenomenex C8 column(30 mm×2.00 mm,3μm)with gradient elution using water-methanol as mobile phase. Electrospray ionization(ESI)was adopted in the negative ion mode for multiple reaction monitoring(MRM). The mass transitions were m/z 577.6→269.1 for rhoifolin,and m/z 271.0→151.0 for naringenin(internal stan?dard),respectively. Results The method showed good linearity over the range of 1-2000μg/L. Intra and inter-day precisions were both less than 10%,the relative error was within ± 7%. The extraction recoveries of three concentrations (low,middle and high) ranged from 86.8%to 91.0%. Main pharmacokinetic parameters were calculated by DAS 2.0. AUC0-t was(72627.8± 18067.9)μg·min/L, t1/2 was(52.1±14.3)min and CLz was(0.07±0.02)L/(min·kg). Conclusion The established LC-MS/MS method is specific and sensi?tive,and can be applied to pharmacokinetic study of rhoifolin. The pharmacokinetic parameters show that rhoifolin is eliminated rapid?ly in rats.