Serum lithium determination

A5. Amdisen, A., Serum lithium determinations for clinical use. Scand. J. Clin. Lab. Invest. 20, 104-108 (1967). 

L8. Levy, A. L., and Katz, E. M., A comparison of serum lithium determinations using flame photometry and atomic absorption spectrophotometry. Clin. Chem. 16, 840-842 (1970). 

Vll. Villeneuve, A., Dery, R., and Genest, P. H., A simple micromethod for serum lithium determination. Clin. Biochem. 4, 194-195 (1971). 

Toxicity is closely related to serum lithium levels and can occur at therapeutic doses. Facilities for serum lithium determinations are required to monitor therapy. 

With normal renal function, all that may be necessary is watchful waiting, careful monitoring of the clinical status, and repeated serum lithium determinations. 

The inadvertent use of lithium heparin as an anticoagulant in the collection tube will lead to a spuriously high serum lithium determination. 

Measuring erythrocyte lithium concentrations does not appear to offer any advantages over serum lithium determinations in the management of lithium toxicity [94 ]. 

Indications and Dosages Alert During acute phase, a therapeutic serum lithium concentration of 1-1.4 mEq/L is required. For long-term control, the desired level is 0.5-1.3 mEq/L. Monitor serum drug concentration and clinical response to determine proper dosage. 

An initial determination of serum lithium concentration should be obtained about 5 days after the start of treatment, at which time steady-state conditions should have been attained. If the clinical response suggests a change in dosage, simple arithmetic (new dose equals present dose times desired blood level divided by present blood level) should produce the desired level. The serum concentration attained with the adjusted dosage can be checked after another 5 days. Once the desired concentration has been achieved, levels can be measured at increasing intervals unless the schedule is influenced by intercurrent illness or the introduction of a new drug into the treatment program. 

Lithium is easily, inexpensively, and accurately measurable in the serum, and serum concentration determination is a useful adjunct to monitoring its therapeutic efficacy and avoiding toxicity (54). 

Routine serum lithium estimations on blood taken 12 hr after the previous dose give no indication of the peak serum lithium concentrations. These usually occur within 4 hr of the dose and are associated with any transient side effects that may occur (50). The pharmacokinetics of lithium preparations is studied by administration of a single test dose of the drug followed by timed sequential blood lithium determinations. Such studies are of interest for the following reasons ... 

Sodium and potassium in serum are determined in the clinical laboratory by atomic-emission spectroscopy, using an instrument designed specifically for this purpose [5]. Two filter monochromators isolate the sodium and potassium emission lines. A lithium internal standard is used, and the ratios of the Na/Li and K/Li signals are read out on two separate meters. The internal standard compensates for minor fluctuations in flame temperature, aspiration rate, and so forth. A cool flame, such as air-propane, is used to minimize ionization. Typically, the serum sample and standards are diluted 1 200 with a 100 ppm Li solution and aspirated directly. The instrument can be adjusted to read directly in meq/1 for sodium and potassium by adjusting the gain while aspirating appropriate standards. 

Table 3 summarizes those elements determined at levels exceeding the physiological concentrations. Bowman 96) determined 0.3 ppm lithium in serum by 1 10 dilution, and by adding sodium and potassium to standards. The concen-... 

Oxalate does not interfere with glucose assays, but insulin values determined in oxalate-plasma are lower than those obtained with lithium heparin-plasma or serum (L6). Specimens collected in EDTA demonstrate lower carbon dioxide combining power than those observed with serum or heparin or potassium oxalate plasma (Zl). 

Figure 5.23 — Flow-through ionophore-based sensor for the determination of lithium in serum. (A) Mechanism involved in the sensor response (symbol meanings as in Fig. 5.20). (B) Diffuse reflectance flow-cell (a) upper stainless steel cell body (A) silicon rubber packing (c) quartz glass window (d) Teflon spacer (0.05 mm thickness) (e) hydrophobic surface mirror (/) lower stainless steel cell body. For details, see text. (Reproduced from [90] with permission of the American Chemical Society).

Serum concentrations required for prophylaxis are not as well determined. The only controlled trial of patients randomly assigned to a low lithium level (0.4—0.6 mEq/L) compared with a standard-... 

When a specific antidote or other treatment is under consideration, quantitative laboratory testing may be indicated. For example, determination of the acetaminophen serum level is useful in assessing the need for antidotal therapy with acetylcysteine. Serum levels of salicylate (aspirin), ethylene glycol, methanol, theophylline, carbamazepine, lithium, valproic acid, and other drugs and poisons may indicate the need for hemodialysis (Table 58-3). 

To determine the safety of using lithium chloride dilution to measure cardiac output, the pharmacokinetic and toxic effects of intravenous lithium chloride have been studied in six conscious healthy Standardbred horses (527). The mean peak serum concentration was 0.56 mmol/1. There were neither toxic effects nor significant changes in laboratory studies, electrocardiograms, or gastrointestinal motility. Three horses had increased urine output. 

Wilting I, Movig KL, Moolenaar M, Hekster YA, Brouwers JR, Heerdink ER, Nolen WA, Egberts AC. Drug-drug interactions as a determinant of elevated lithium serum levels in daily clinical practice. Bipolar Disord 2005 7 274-80. 

It has been long recognized that prolonged lithium therapy can cause hypothyroidism. In fact, determination of serum thyroid-stimulating hormone once a year is recommended in all subjects on prolonged lithium therapy [32, 33]. Lithium perturbs receptor-mediated signaling events such as cyclic adenosine monophosphate and inositol phosphate accumulation [34]. These effects likely explain many hormonal side effects of lithium. 

The concentration of lithium in serum, plasma, urine, or other body fluids has been determined by flame emission photometry, atomic absorption spectrometry, or electro-chemically using an ion-selective electrode. Serum analysis, the most useful specimen for lithium monitoring, is most commonly quantified by automated spectrophotometric assay. 

Formazan reagents are highly selective to lithium. The use of formazan enables the determination of Li in the presence of a 5,000-fold excess of Na, which is of importance in the determination of Li in blood [49,50]. Lithium was determined also with another reagent from this group, (e = 2.0-10 ) [51]. Quinizarine was used for determination of Li in drugs and in blood serum [52]. 

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