Validation Method for Blood and Saliva Lithium Determination: Application for Therapeutic Drug Monitoring by Atomic Absorption Spectrophotometry

Abstract

Background: Lithium is an effective medication used as first-line therapy for bipolar disorder. Due to its narrow therapeutic index, frequent monitoring is highly recommended. Objective: This study was designed to validate the atomic absorption spectrophotometric method for serum and saliva lithium determination and examine its application for lithium therapeutic monitoring in patients with bipolar affective disorder. Methods: The atomic absorption spectrophotometer (AAS) apparatus (Rayleigh, China) analyzes lithium in human blood and saliva samples. Precision, Recovery % (Accuracy), Detection Limit, and Specificity were evaluated to validate the used analysis method. The patient's study design was based on an observational study, where four patients with bipolar disorders type 1 and 2 (adults with bipolar disorder and on lithium therapy for one month) aged 32 to 64 years and weighing from 56 to 92 kg participated in this study. Four samples were collected from each patient, two samples of blood and another two of saliva. Results: A linear relationship between the absorbance and lithium concentrations was obtained in 0.175 - 7 μg/mL with an R2 of 0.99. Precision, Recovery % (Accuracy), Detection Limit, and Specificity are within the accepted limits. Ratio analysis of (Saliva/Blood) of Cmin, Cmax, and Cpss were 2.64, 3.77, and 3.54, respectively. The salivary lithium therapeutic range was 2.83- 4.25 mmol/L, which is much higher than blood. Only lithium Cmax in saliva was slightly affected by Body mass index (BMI), age, and creatinine clearance (CLcr), suggesting insignificant effects on lithium levels in general. Conclusions: The AAS method used in this study is reliable and accurate for determining serum and saliva lithium concentrations. A higher correlation coefficient between lithium in saliva and blood suggests that saliva is an excellent candidate to replace blood for lithium therapeutic drug monitoring.