Dried Blood Spots and Miniaturized Ultrasonic Nebulization Microplasma Optical Emission Spectrometry for Point-of-Care Testing of Blood Lithium.

Despite the significant importance of blood lithium (Li) detection in the treatment of bipolar disorder (BD), its point-of-care testing (POCT) remains a great challenge due to tedious sample preparation and the use of large-footprint atomic spectrometers. Herein, a system coupling dried blood spots (DBS) with a point discharge optical emission spectrometer equipped with a miniaturized ultrasonic nebulizer (MUN-µPD-OES) was developed for POCT of blood Li. Three microliters of whole blood were used to prepare a dried blood spot on a piece of filter paper to which 10 µL of eluent (1% (v/v) formic acid and 0.05% (v/v) Triton-X) was added. Subsequently, the paper was placed onto the vibrating steel membrane of the ultrasonic nebulizer and powered on to generate aerosol. The aerosol was directly introduced to the µPD-OES for quantification of Li by monitoring its atomic emission line at 670.8 nm. The proposed method minimized matrix interference caused by high levels of salts and protein. It is worth noting that the MUN suitably matches the needs of DBS sampling and can provide aerosolized introduction of Li into the assembled µPD-OES, thus eliminating all tedious sample preparation and the need for a commercial atomic spectrometer. Calibration response is linear in the therapeutic range and a limit of detection (LOD) of 1.3 µg L-1 is well below the Li minimum therapeutic concentration (2800 µg L-1). Li in mouse blood was successfully detected in real-time using MUN-µPD-OES after intraperitoneal injection of lithium carbonate, confirming that the system holds great potential for POCT of blood Li for patients with BD.

Existing and Emerging Technologies for Therapeutic Monitoring of Lithium: A Scoping Review.

BACKGROUND/PURPOSE: Lithium is an effective psychoactive drug. It has a narrow therapeutic margin, with subtherapeutic levels or intoxication commonly occurring. Therapeutic drug monitoring (TDM) of lithium has several barriers. This scoping review aims to describe and analyze existing and emerging technologies for lithium TDM and to describe the lithium quantification parameters (precision, accuracy, detection limit) attributed to each technology. METHOD: PubMed, Scopus, Web of Science, and Google Scholar were searched. Studies that described lithium quantification and complied with PRISMA-ScR guidelines were included. Articles selection was conducted by 2 researchers. Good precision was defined if its relative standard deviation <3%; acceptable, from 3% to 5%; and low, >5%. Accuracy was considered good if the error <5%; acceptable, 5%1 to 0%; and low if it was >10%. RESULTS: Of the 2008 articles found, 22 met the inclusion criteria. Of these, 14 studies concerned laboratory devices, in which precision was found to be low in one third of cases, and half had good precision. Accuracy of one third was good, another third was low, and the remaining third did not report accuracy. The other 8 studies concerned portable devices, in which precision was low in more than 60% of the cases and good in 25% of the studies. Accuracy was low in 50% of the cases, and good in just over a third. Limits of detection included the therapeutic range of lithium in all studies. CONCLUSIONS: Among emerging technologies for lithium TDM, precision and accuracy remain a challenge, particularly for portable devices.

Effects of Plasmapheresis on Serum Lithium Levels in an ICU Patient with Bipolar Disorder: A Case Study.

ABSTRACT: This is a case description of a patient with bipolar disorder undergoing lithium therapy who received plasmapheresis for neuromyelitis optica spectrum disorder. Plasmapheresis resulted in lower and subtherapeutic serum lithium levels. Using therapeutic drug monitoring, a dose escalation of 80% was necessary to maintain therapeutic serum lithium levels. This underscores the importance of individualized therapy through therapeutic drug monitoring.

Genetic background determines renal response to chronic lithium treatment in female mice.

Chronic lithium treatment for bipolar disease causes mainly side effects in the kidney. A subset of lithium users develops nephrogenic diabetes insipidus (NDI), a urinary concentrating disorder, and chronic kidney disease (CKD). Age, lithium dose, and duration of treatment are important risk factors, whereas genetic background might also play an important role. To investigate the role of genetics, female mice of 29 different inbred strains were treated for 1 year with control or lithium chow and urine, blood, and kidneys were analyzed. Chronic lithium treatment increased urine production and/or reduced urine osmolality in 21 strains. Renal histology showed that lithium increased interstitial fibrosis and/or tubular atrophy in eight strains, whereas in none of the strains glomerular injury was induced. Interestingly, lithium did not elevate urinary albumin-creatinine ratio (ACR) in any strain, whereas eight strains even demonstrated a lowered ACR. The protective effect on ACR coincided with a similar decrease in urinary IgG levels, a marker of glomerular function, whereas the adverse effect of lithium on interstitial fibrosis/tubular atrophy coincided with a severe increase in urinary ß2-microglobulin (ß2M) levels, an indicator of proximal tubule damage. Genetic background plays an important role in the development of lithium-induced NDI and chronic renal pathology in female mice. The strong correlation of renal pathology with urinary ß2M levels indicates that ß2M is a promising biomarker for chronic renal damage induced by lithium.

Relationship between serum lithium concentration and kidney damage in a preclinical model.

OBJECTIVES: The aim of the present study was to assess whether there is a relationship between serum lithium concentrations and the magnitude of kidney damage in a preclinical model. METHODS: Thirty Wistar male rats were randomized into three groups: control group fed ad libitum powered standard diet for 3 months; and experimental groups fed ad libitum the same diet supplemented with 30 or 60 mmol/kg diet for 3 months (LowLi and HighLi groups respectively). Laboratory parameters were assessed at months 1 and 3 and histopathological changes were evaluated after 3 months. RESULTS: Serum lithium levels in experimental rats were within therapeutic range used in humans throughout the entire experiment. After 3 months of treatment, lithium levels were statistically higher in HighLi group. Rats of the LowLi group showed dilation of cortical tubules although with similar clearance of creatinine. Rats from the HighLi group had greater histopathological damage in addition to lower creatinine clearance than the other two groups. CONCLUSIONS: Our study suggests that during long-term treatments, even with serum lithium levels within the therapeutic range used in humans, the risk of kidney damage could increase proportionally to the serum lithium concentration.

Drug-Drug Interactions Between Lithium and Cardiovascular as Well as Anti-Inflammatory Drugs.

INTRODUCTION: Lithium is the gold standard in treating bipolar affective disorders. As patients become increasingly older, drug-drug interactions leading to decreased excretion of lithium represent a key issue in lithium safety. As no study considered the effect of comedications on lithium serum concentration in combination, we aimed to quantify the impact of drugs affecting renal blood flow and function and thus potentially interacting drugs (diuretics, ACE inhibitors, AT1 antagonists, and non-steroidal anti-inflammatory drugs) on lithium serum levels in addition to age, sex, and sodium and potassium serum levels as well as renal function. METHODS: Retrospective data of lithium serum levels were analyzed in 501 psychiatric inpatients (2008-2015) by means of linear regression modelling. RESULTS: The number of potentially interacting drugs was significantly associated with increasing serum levels of lithium in addition to the established factors of age, renal function, and sodium concentration. Additionally, absolute lithium levels were dependent on sex, with higher values in females. However, only NSAIDs were identified to increase lithium levels independently. DISCUSSION: Routine clinical practice needs to focus on drugs affecting renal blood flow and function, especially on NSAIDs as over-the-counter medication that may lead to an increase in lithium serum concentration. To prevent intoxications, clinicians should carefully monitor the comedications, and they should inform patients about possible intoxications due to NSAIDs.

Derivation of whole blood biomonitoring equivalents for lithium for the interpretation of biomonitoring data.

INTRODUCTION: Lithium salts have numerous industrial uses and are also used in the treatment of bipolar disorders. The main source of lithium exposure to the general population is drinking water and foods. Lithium is nephrotoxic at higher doses. Thus, oral exposure guidelines for lithium have been derived, including ICH's permitted daily exposure (PDE = 0.008 mg lithium/kg-bw/day) adopted by Health Canada and the United States Environmental Protection Agency's (U.S. EPA) provisional peer reviewed toxicity value (PPRTV = 0.002 mg lithium/kg-bw/day), both based on human data. OBJECTIVE: To derive whole blood biomonitoring equivalents (BEs) associated with PDE and PPRTV to interpret population-level biomonitoring data in health risk context. METHOD: A simple kinetic relationship based on plasma clearance value (0.5 L/kg-bw/day) and the oral absorption fraction (100%) was used to derive blood BEs for PDE and PPRTV. RESULTS: This analysis resulted in BE values in plasma and whole blood of 16 and 10 µg/L, respectively, based on the PDE values developed by the Health Canada and of 4.2 and 2.7 µg/L, respectively, based on the PPRTV developed by U.S. EPA. CONCLUSION: The derived BE values can be used to interpret population-level biomonitoring data.

Circulating metal concentrations, inflammatory cytokines and gestational weight gain: Shanghai MCPC cohort.

OBJECTIVES: Based on a prospective birth cohort, we aimed to investigate the associations between maternal circulating metals exposure and gestational weight gain (GWG) across pregnancy, and explore whether maternal inflammatory cytokines could contribute to the GWG changes associated with metals exposure. METHODS: A total of 234 pregnant women from the Shanghai Maternal-Child Pairs cohort were enrolled in this panel study. 547 blood and serum samples were collected from pregnant women during three follow-up visits, and the circulating concentrations of 27 metals were determined by using the ICP-MS method. Five inflammatory cytokines in serum samples were measured through multiplexed immunoassays. The linear mixed models were used to estimate the association between each ln-transformed metal concentration and GWG across pregnancy. Robust generalized linear regression models were used to estimate the associations among circulating metals, GWG, and inflammatory cytokines. RESULTS: The GWG during pregnancy was 13.76 ± 1.40 kg. The concentrations Co, Zn, Mo, B, Ag and Te in second or third trimesters were significantly higher than those in early second trimester. The concentration of Mg decreased with the increase of pregnant weeks and no significant statistical differences were found in the concentrations of other metals in different trimesters. Among the detected 26 metals, Li and Sr concentrations were positively associated with GWG in the third trimester. The GWG increased by 0.100 kg (95% CI 0.005, 0.195) and 0.120 kg (95% CI 0.009, 0.232) with each one ln-concentration increase in circulating Li and Sr concentrations, respectively. Concentrations of Li and Sr in the third trimester were positively associated with tumor necrosis factor-alpha (TNF-α) and interleukin (IL)-6, but negatively associated with growth differentiation factor-15 (GDF-15) significantly. Besides, IL-6 and GDF-15 levels were associated with the increase or decrease of overall pregnancy GWG, respectively. CONCLUSIONS: Results showed that maternal exposure to Li and Sr were associated with increased GWG, in which maternal IL-6 and GDF-15 could contribute to the associations between metal exposures and GWG in pregnant women.

Chemical Imaging in Vivo: Photoacoustic-Based 4-Dimensional Chemical Analysis.

We describe how 4-dimensional in vivo biochemical analysis can be performed using photoacoustic contrast nanoagents that have been designed to probe both structural and chemical information in vivo, enabling noninvasive, real time, spatially resolved chemical imaging. Early chemical imaging of a patient's tumor can inform the decision of effective treatment, regarding choices of chemotherapy, radiation, or immunotherapy.

Safety monitoring of treatment in bipolar disorder in a tertiary care setting in Sri Lanka and recommendations for improved monitoring in resource limited settings.

BACKGROUND: Safety monitoring of medicines is essential during therapy for bipolar disorder (BD). We determined the extent of safety monitoring performed according to the International Society for Bipolar Disorders (ISBD) guidelines in patients with BD attending the main tertiary care psychiatry clinics in Sri Lanka to give realistic recommendations for safety monitoring in resource limited settings. METHODS: Patients diagnosed with BD on mood stabilizer medications for more than 1 year were recruited. Data were collected retrospectively from clinic and patient held records and compared with the standards of care recommended by ISBD guidelines for safety monitoring of medicines. RESULTS: Out of 256 patients diagnosed with BD, 164 (64.1%) were on lithium. Only 75 (45.7%) had serum lithium measurements done in the past 6 months and 96 (58.5%) had concentrations recorded at least once in the past year. Blood urea or creatinine was measured in the last 6 months only in 30 (18.3%). Serum electrolytes and thyroid-stimulating hormone (TSH) concentrations were measured in the last year only in 34 (20.7%) and 30 (18.3%) respectively. Calcium concentrations were not recorded in any patient. None of the patients on sodium valproate (n = 119) or carbamazepine (n = 6) had blood levels recorded to establish therapeutic concentrations. Atypical antipsychotics were prescribed for 151 (59%), but only 13 (8.6%) had lipid profiles and only 31 (20.5%) had blood glucose concentration measured annually. Comorbidities experienced by patients influenced monitoring more than the medicines used. Patients with diabetes, hypothyroidism and hypercholesterolemia were more likely to get monitored for fasting blood glucose and (p < 0.001), TSH (p < 0.001) and lipid profiles (p < 0.001). Lithium therapy was associated with TSH monitoring (p < 0.05). Therapy with atypical antipsychotics was not associated with fasting blood glucose or lipid profile monitoring (p > 0.05). A limitation of the study is that although some tests were performed, the results may not have been recorded. CONCLUSIONS: Safety monitoring in BD was suboptimal compared to the ISBD guidelines. ISBD standards are difficult to achieve in resource limited settings due to a multitude of reasons. Realistic monitoring benchmarks and recommendations are proposed for methods to improve monitoring in resource limited settings based on our experience.

Evaluation of BD Barricor™ Plasma Blood Collection Tube for Biochemical Tests.

BACKGROUND: Blood from patients who are receiving anticoagulant therapy may take longer to clot. Anticoagulation is an important component of the dialysis prescription. We compared BD Vacutainer® Barricor™ Plasma Blood Collection Tubes (BD BarrricorTM), BD Vacutainer® PST™ Lithium Heparin Tubes (BD PST™), and BD (Becton-Dickinson, Franklin Lakes, NJ, USA) Vacutainer Serum Separator Tubes (BD SST), as reference tube in dialysis patients to examine whether they had an effect on routine biochemical tests. MATERIALS AND METHODS: A total of 29 chronic hemodialysis patients were included in this study. Samples were collected into BD BarrricorTM, BD PST™, and BD SST tubes after the dialysis. All the tubes were centrifuged by NF 1200R rotor (1,300 g for 10 minutes at 22°C, 1,200 g for 10 minutes at 4°C, 2,400 g for 10 minutes at 22°C, respectively) after the incubation period. Eleven routine clinical chemistry parameters (Creatinine, Urea, Na, K, Cl, AST, ALT, Total Bilirubin, Direct Bilirubin, Calcium, Cholesterol) were analyzed on a Beckman Coulter AU 5800. RESULTS: Results of creatinine, K and cholesterol were statistically significantly different between the SST and LiH (p = 0.014, p = 0.009, and p < 0.001, respectively). In terms of other biochemical parameters we tested for all three tubes there was no clinically significance inspite of the statistically significance. CONCLUSIONS: BD Barricor™ tubes provide fast, clean, high-quality plasma samples, safe results, and may lower times and costs.

Risk-Benefit assessment of infant exposure to lithium through breast milk: a systematic review of the literature.

The continuation of lithium while breastfeeding is a controversial topic, and clinical recommendations vary. A systematic review was completed of available data on lithium and breastfeeding to determine the degree of lithium exposure through breast milk and assess the potential risk to the infant. Databases, including PubMed MEDLINE, Embase, PsycINFO, Web of Science, Scopus, and Cochrane CENTRAL Register of Controlled Trials databases, were searched for articles on lithium and breastfeeding from the start dates of the databases through December 2018. Articles were included if the report included at least one maternal serum/plasma and/or breast milk lithium concentration and one infant serum/plasma lithium concentration. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. Twelve articles, all case reports, were selected for inclusion out of 441 articles that were found and 230 that were reviewed from the search. Data are limited on the safety of lithium continuation while breastfeeding. Among the adverse effects reported, it is difficult to differentiate poor outcomes from factors affecting infant health, concomitant medications, and gestational lithium exposure. Recommendations on whether to continue lithium while breastfeeding must be personalized to the individual woman and her infant.

Stability of routine biochemical analytes in whole blood and plasma/serum: focus on potassium stability from lithium heparin.

BACKGROUND: Blood specimens are transported from clinical departments to the biochemistry laboratory by hospital courier service, sometimes over long distances. The aim of this study was to assess the stability of common biochemical analytes in venous blood under our routine transport conditions and to evaluate analyte stability after prompt or delayed centrifugation. METHODS: We investigated pre- and postanalytical contributions of 32 biochemical analytes in plasma and serum samples from 10 patients (healthy adults and patients from intensive care units). Differences in analyte concentrations between baseline (T0) and different time intervals (2, 4, 6, 8, 12 and 24 h) following storage after prompt and delayed centrifugation were reported. Evaluation was against the total change limit as described by Oddoze et al. (Oddoze C, Lombard E, Portugal H. Stability study of 81 analytes in human whole blood, in serum and in plasma. Clin Biochem 2012;45:464-9). RESULTS: The majority of analytes were stable with delayed separation up to 12 h, except for potassium, C-peptide, osteocalcin, parathyroid hormone (PTH), bicarbonate and LDH. After prompt centrifugation and storage at 4°C, stability was greatly increased up to 48 h for most analytes. LDH and bicarbonate had the lowest stability after centrifugation; therefore, no reanalysis of these analytes in a centrifuged tube can be allowed. CONCLUSIONS: Knowledge of analyte stability is crucial to interpret biological analysis with confidence. However, centrifugation prior to transport is time consuming, and the transfer of plasma or serum from a primary tube to a secondary tube increases the risk of preanalytical errors. For analytes that are stable in whole blood for 24 h or more, it seems that there is no benefit to centrifuge before transport.

Prediction Model of Serum Lithium Concentrations.

INTRODUCTION: Therapeutic drug monitoring is necessary for lithium, but clinical application of several prediction strategies is still limited because of insufficient predictive accuracy. We herein proposed a suitable model, using creatinine clearance (CLcr)-based lithium clearance (Li-CL). METHODS: Patients receiving lithium provided the following information: serum lithium and creatinine concentrations, time of blood draw, dosing regimen, concomitant medications, and demographics. Li-CL was calculated as a daily dose per trough concentration for each subject, and the mean of Li-CL/CLcr was used to estimate Li-CL for another 30 subjects. Serum lithium concentrations at the time of sampling were estimated by 1-compartment model with Li-CL, fixed distribution volume (0.79 L/kg), and absorption rate (1.5/hour) in the 30 subjects. RESULTS: One hundred thirty-one samples from 82 subjects (44 men; mean±standard deviation age: 51.4±16.0 years; body weight: 64.6±13.8 kg; serum creatinine: 0.78±0.20 mg/dL; dose of lithium: 680.2±289.1 mg/day) were used to develop the pharmacokinetic model. The mean±standard deviation (95% confidence interval) of absolute error was 0.13±0.09 (0.10-0.16) mEq/L. DISCUSSION: Serum concentrations of lithium can be predicted from oral dosage with high precision, using our prediction model.

Nonlinear disposition of lithium in rats and saturation of its tubular reabsorption by the sodium-phosphate cotransporter as a cause.

We previously reported the contribution of sodium-phosphate cotransporter to the tubular reabsorption of lithium in rats. In the present study, the dose dependency of the renal handling of lithium was examined in rats. When lithium chloride at 1.25 mg/kg, 2.5 mg/kg and 25 mg/kg was intravenously injected as a bolus, the areas under the plasma concentration-time curve of lithium until 60 minutes were calculated to be 6.23 mEq·min/l, 8.77 mEq·min/l and 64.6 mEq·min/l, respectively. The renal clearance of lithium and its fractional excretion increased with increments in the dose administered. The renal clearance of lithium strongly correlated with the urinary excretion rate of phosphate in the 1.25 mg/kg group (r = 0.840) and 2.5 mg/kg group (r = 0.773), whereas this correlation was weak in the 25 mg/kg group (r = 0.306). The infusion of foscarnet, a typical inhibitor of sodium-phosphate cotransporter, decreased the fractional reabsorption of lithium in rats administered lithium chloride at 2.5 mg/kg, but did not affect it in rats administered 25 mg/kg. These results demonstrate the nonlinearity of the renal excretion of lithium in rats, with the saturation of lithium reabsorption by the sodium-phosphate cotransporter potentially being involved.

Ghrelin Serum Concentrations Are Associated with Treatment Response During Lithium Augmentation of Antidepressants.

Background: Lithium augmentation of antidepressants is an effective strategy in treatment-resistant depression. The proteohormone ghrelin is thought to be involved in the pathophysiology of depression. The purpose of this study was to investigate the association of treatment response with the course of ghrelin levels during lithium augmentation. Method: Ghrelin serum concentrations and severity of depression were measured in 85 acute depressive patients before and after 4 weeks of lithium augmentation. Results: In a linear mixed model analysis, we found a significant effect of response*time interaction (F1.81=9.48; P=.0028): under treatment, ghrelin levels increased in nonresponders and slightly decreased in responders to lithium augmentation. The covariate female gender had a significant positive effect (F1.83=4.69; P=.033), whereas time, response, appetite, and body mass index (kg/m2) did not show any significant effect on ghrelin levels (P>.05). Conclusion: This is the first study showing that the course of ghrelin levels separates responders and nonresponders to lithium augmentation. Present results support the hypothesis that ghrelin serum concentrations might be involved in response to pharmacological treatment of depression.

Electroencephalographic patterns of lithium poisoning: a study of the effect/concentration relationships in the rat.

OBJECTIVES: Lithium overdose may result in encephalopathy and electroencephalographic abnormalities. Three poisoning patterns have been identified based on the ingested dose, previous treatment duration and renal function. Whether the severity of lithium-induced encephalopathy depends on the poisoning pattern has not been established. We designed a rat study to investigate lithium-induced encephalopathy and correlate its severity to plasma, erythrocyte, cerebrospinal fluid and brain lithium concentrations previously determined in rat models mimicking human poisoning patterns. METHODS: Lithium-induced encephalopathy was assessed and scored using continuous electroencephalography. RESULTS: We demonstrated that lithium overdose was consistently responsible for encephalopathy, the severity of which depended on the poisoning pattern. Acutely poisoned rats developed rapid-onset encephalopathy which reached a maximal grade of 2/5 at 6 h and disappeared at 24 h post-injection. Acute-on-chronically poisoned rats developed persistent and slightly fluctuating encephalopathy which reached a maximal grade of 3/5. Chronically poisoned rats developed rapid-onset but gradually increasing life-threatening encephalopathy which reached a maximal grade of 4/5. None of the acutely, 20% of the acute-on-chronically and 57% of the chronically lithium-poisoned rats developed seizures. The relationships between encephalopathy severity and lithium concentrations fitted a sigmoidal Emax model based on cerebrospinal fluid concentrations in acute poisoning and brain concentrations in acute-on-chronic poisoning. In chronic poisoning, worsening of encephalopathy paralleled the increase in plasma lithium concentrations. CONCLUSIONS: The severity of lithium-induced encephalopathy is dependent on the poisoning pattern, which was previously shown to determine lithium accumulation in the brain. Our data support the proposition that electroencephalography is a sensitive tool for scoring lithium-related neurotoxicity.

Predicting serum drug level using the principles of pharmacokinetics after an overdose: a case of lithium overdose.

OBJECTIVE: In cases of drug overdose, clinicians often find it challenging to predict serum drug level and decide the optimum time for recommencing the overdosed drug. METHOD: This paper describes how to predict serum drug level using the principles of pharmacokinetics. RESULTS: The proposed method and recommencement of the overdosed drug is demonstrated using a clinical case of lithium overdose. CONCLUSION: The proposed method can assist clinicians in predicting serum drug levels and deciding the optimum time for recommencing the overdosed drug safely. Therefore, it may reduce unnecessary repeat serum drug level procedures.

Polyurethane Ionophore-Based Thin Layer Membranes for Voltammetric Ion Activity Sensing.

We report on a plasticized polyurethane ionophore-based thin film material (of hundreds of nanometer thickness) for simultaneous voltammetric multianalyte ion activity detection triggered by the oxidation/reduction of an underlying poly(3-octylthiophene) film. This material provides excellent mechanical, physical, and chemical robustness compared to other polymers. Polyurethane films did not exhibit leaching of lipophilic additives after rinsing with a direct water jet and exhibited resistance to detachment from the underlying electrode surface, resulting in a voltammetric current response with less than <1.5% RSD variation (n = 50). In contrast, plasticized poly(vinyl chloride), polystyrene, and poly(acrylate) ionophore-based membranes of the same thickness and composition exhibited a significant deterioration of the signal after identical treatment. While previously reported works emphasized fundamental advancement of multi-ion detection with multi-ionophore-based thin films, polyurethane thin membranes allow one to achieve real world measurements without sacrificing analytical performance. Indeed, polyurethane membranes are demonstrated to be useful for the simultaneous determination of potassium and lithium in undiluted human serum and blood with attractive precision.