*Corresponding Author:
I. Kuźmicka
Institute of Chemistry, University of Białystok, Hurtowa 1, Białystok 15-399, Poland
E-mail: [email protected]
Date of Submission 21 September 2007
Date of Revision 06 August 2008
Date of Acceptance 12 January, 2009
Indian J Pharm Sci,2009, 71 (1): 8-18  


Psychotropic drugs are an important family of compounds from a medical point of view. Their application in therapy requires methods for the determination in pharmaceutical dosage forms and body fluids. Several methods for their analysis have been reported in the literature. Among the methods, spectrophotometric and electrochemical are very useful for the determination of the drugs. Some of the spectrophotometric methods are based on the formation of the binary and ternary compounds with complexes of metals. The formed compounds are sparingly soluble in water, but quantitatively extracted from aqueous phase into organic solvents and the extracts are intensely colored and stable for a few days. These complexes have been employed in pharmaceutical analysis. The electrochemical procedures are very useful in determination of the psychotropic substances in pharmaceutical preparations.


Psychotropic drugs, spectrophotometric and electrochemical methods, analysis


Psychotropic drugs belong to a large group of organic compounds. They exhibit high activity and manysided pharmacological actions. Owing to these properties, they have been subject of extensive pharmacological studies. Typical psychotropic drugs are often prescribed in severe cases of schizophrenia or depression, when new generation neuroleptics and SSRI medications do not work. Typical tricyclic psychotropic drugs are characterized by a tricyclic rings and presence of sulfur and nitrogen atoms. Structures of select psychotropic drugs of both typical and atypical type are presented in fig. 1.


Fig. 1: Formulae of antipsychotic drugs Formulae of dibenzoazepines (I), thioxanthenes (II), azaphenothiazines (III) phenothiazines (IV), olanzapine (V), trazodone (VI), sertraline (VII), paroxetine (VIII), fluoxetine (IX), fluvoxamine (X)

Tricyclic psychotropic drugs due to their characteristic structure – the presence of chemically active sulfur and nitrogen atoms and substituents react with oxidants (e.g. Os(VIII), Cr(VI), V(V), Ce(IV), Au(III), Fe(III)), platinum metals (e.g. Pt(IV), Rh(IV), Ru(III), Pd(II)), thiocyanate or halide complexes of metals and some organic substances (e.g. picric acid, alizarin S, dipicrylamine) [1-6]. The above mentioned reactions are very important from an analytical point of view.

The liability of phenothiazines, thioxantenes and dibenzoazepines to the oxidation in acid medium by K2Cr2O7, NH4VO3, Ce(SO4)2 has been exploited as indicators in various redox titrations [5,7] and as reagents for the spectrophotometric determination of the drugs [8-10].

The new generation psychotropic drugs, e.g., fluoxetine, fluvoxamine and trazodone react with some organic compounds such as chrome azurol S, eriochrome cyanine R, bromophenol blue, methyl orange, bromocresol green and thymol blue to form ion-association compounds [11-16]. These properties have been exploited for the development of spectrophotometric methods for the determination of the psychotropic drugs.

Atypical psychotropic drugs can also easily reduced on mercury electrode [17,18]. Mechanism of electrochemical reactions of these compounds was investigated using different electrochemical methods, e.g. cyclic voltammetry and differential pulse voltammetry [19]. Electrochemical behaviour of these substances can be successfully employed for elaborate simple, rapid and sensitive procedures for the determination of new psychotropic drugs in pharmaceutical preparations and biological fluids.

In the presented review the analytical applications of the reactions of psychotropic drugs with organic substances and thiocyanate complexes of metals for the spectrophotometric determination of the drugs have been described. This review is also devoted to the analytical application of the electrochemical methods for their determination.

Binary and ternary complexes of psychotropic drugs

Psychotropic substances, e.g. phenothiazines, dibenzocycloheptadienes and thioxantenes react with organic substances, which occur as anions in aqueous solutions forming colored ion-association binary compounds [20]. These compounds are insoluble into organic solvents, e.g. chloroform, butanol and benzene. The extracts are intensely colored and very stable (1-3 days) [21]. These properties were applied successfully for the spectrophotometric determination of psychotropic drugs [21-41] (Table 1).

Psychotropic drugs Organic reagents Organic solvent λ [nm] ε [l·-mol-1cm-1] Range of determination [ppm] Ref.
Perphenazine Dipicrylamine chloroform 420 1.09·104 8 – 60 21
Chlorpromazine   chloroform 420 3.22·104 0.7 - 7 22
Thioproperazine     435 1.51·104 1.6-16  
Chlorpromazine Alizarin S chloroform 420 8.00·103 7 – 70 23
Promethazine   chloroform 420 8.50·103 7 - 70 24
Chlorpromazine Brilliant  blue chloroform 620 2.21·104 1 – 10 25
Fluphenazine       1.02·104 2 - 10  
Thioridazine       2.78·104 1 - 10  
Levomepromazine Bromophenol blue chloroform 409 - 5 - 25 26
Fluoxetine Chrome chloroform 500 1.02·104 5-50 12
Fluvoxamine Azurol S chloroform- 502 9.05·103 7-100  
    butanol (3:1)        
Chlorpromazine   chloroform 510 1.48·104 2 – 20 27
Promethazine       2.04·104 1 – 12  
Thioproperazine     460 1.57·104 2 – 28 28
Trifluopromazine       2.12·104 1 – 12  
Promethazine Methyl orange chloroform - - 20–100 29
Imipramine Eriochrome butanol 520 4.80·103 10 - 80 30
  Cyanine R          
Chlorpromazine Pyrocatechol chloroform - 445 1.04·104 3.5 – 35 31
Chlorprothixene violet butanol (5:1)        
    chloroform – 445 1.40·104 3.5 - 32 32
    butanol (5:1)        
Chlorpromazine Flavianic acid benzene 390 9.60·103 7– 70 33
Thioridazine     385 - 5 – 20 34
Promazine Picramic acid chloroform 500 2.10·103 8 – 80 35
Thioproperazine       - 16 – 160 36
Thioridazine Picric acid benzene 405 - 20 – 70 34
Thioproperazine     406 7.30·103 10 - 80 33
Trifluoperazine     406 6.70·103 10 – 100 37
Perphenazine     407 7.60·103 4-80 21
Promazine     405 - 10-60 38
Promethazine Orange II dichloro-methane 485 - 5 – 20 25
Fluphenazine       1.02·104 3 – 25  
Prochlorpromazine   chloroform 495 5.40·104 30-130  
Trifluoperazine       1.14·104 3 – 25 39
Nortriptyline   chloroform 490 - -  
Chlorpromazine Bromocresol green chloroform 420 2.63·104 2 – 8 40
Trifluorpromazine       2.02·104 2 -10  
Thioproperazine       2.65·104 2 -12  
Thioridazine       2.13·104 2 -18  
Chlorpromazine Titanium yellow ethyl acetate 405 - 10 - 60 41
Fluoxetine Eriochrome butanol 520 1.7·104 2-30 13
Fluvoxamine cyanine R   518 6.5·103 2-40  
Trazodone Bromophenol blue chloroform 414 - 3.75-14 11

Table1: Determinationofpsychotropicdrugs in binarysystems

Significant advantages of the spectrophotometric methods are that they can be applied to the determination of individual components in a multicomponent mixture. This aspect of spectrophotometric analysis is of major interest in pharmacy, since it offers distinct possibilities in the assay of a particular component in a complex dosage formulation. For example in the spectrophotometric method elaborated by Basavaiah [40], the commonly used additives and excipients in the dosage forms of active compounds, such as starch, lactose, glucose, sugar, talc, gelatin, magnesium stearate, sodium lauryl sulphate, sodium sulphite, sodium chloride, calcium chloride, ethanol, formaldehyde and sodium salt of EDTA did not interfere in the analysis.

It has been pointed out in our previous papers [2,4,42] that active substances of psychotropic drugs (PS), which occur in an aqueous solution as large cation, PS·HCl⇄(PS·H)++Cl-, or base, PS+H+⇄(PS·H)+, react with some thiocyanate and halide complexes of metals forming ion-association compounds, (m-n) (PS·H)++ [MeXn](m-n)-⇄(PS·H)(m-n) [MeXn], where, Me denotes metal ion with an n-oxidation state (e.g. Co(II), Cd(II), Hg(II), Pd(II), Fe(III), Cr(III), Ti(IV), Pt(IV), Re(IV), Nb(V), Mo(V), W(V), U(VI)); X- SCN- or halide ion. These compounds exhibit a number of properties very important from the analytical view-point, i.e, a well-defined composition and high molecular weight. They are hardly soluble in water but fairly soluble in acetone, methanol, ethanol. They can be extracted from aqueous phase with chloroform and other organic solvents. The extracts are intensely colored and stable for a few days [2]. These properties have been used for the development of the spectrophotometric methods for the determination of psychotropic drugs.

Structures of binary and ternary complexes of psychotropic drugs

The compositions of binary and ternary complexes of psychotropic drugs, e.g., dibenzoazepines, dibenzocycloheptadienes, thioxanthenes, phenothiazines were established by Job`s continuous variation method and by spectrophotometric titration. These compositions are described in the literature [2,4,43,44]. The absorption spectra of the compounds obtained in the UV/VIS and IR-region have been recorded. It was found the main absorption bands of the components are observed in UV-VIS spectra of the compounds [2,43,45]. Infrared spectra of the compounds studied were recorded (KBrdisc) in the region of 400-4000 cm-1 [2,27,45,46]. Significant changes in the spectra were observed in the region of 2300-3700 cm-1. For example, the wide bands, appearing in the phenothiazines spectra in the region of 2300-2700 cm-1 and characteristic for vibration of ≡NH+ group, were shifted (~350 cm-1) towards higher frequencies in the spectra of the compounds. On the basis of the data obtained, it has been established that the compounds studied are ionassociates. For example, the structure of the compound promazine with flavianic acid and compound obtained in Pd(II) - I- - DT system can be presented as follows (Schemes 1 and 2).


Scheme 1: Possible structure of promazine-flavianic acid compound


Scheme 2: The reaction of diethazine hydrochloride with [PdI4]2- The reaction of the protonated amine nitrogen of diethazine hydrochloride with the anionic complex of [PdI4]2-

Spectrophotometric methods

Reviews of the methods for the determination of phenothiazines presented by Blažek [47], Fairbrother [48] and Puzanowska-Tarasiewicz [49] show that spectrophotometric methods are very useful for the determination of psychotropic substances in pharmaceuticals and body fluids [50-56]. They are summarized in Table 2.

Psychotropicsubstance [ppm] Systemsolvent Organic [nm] λ [l·mol-1cm-1] Εdetermination Range of Ref.
Levomepromazine (LPZ) LPZ- [Cr(NH3 )2 (SCN)4 ] acetone 525 9.12·10-4 53 – 427 45
Chlorpromazine (CPZ) CPZ- [Cr(NH3 )2 (SCN)4 ] acetone 520 9.12·10-4 156 – 689 50
Chlorpromazine (CPZ) Fe(III)-SCN--CPZ chloroform 490 - 120 - 300 51
Levomepromazine (LPZ) Fe(III)-SCN-- LPZ 140 - 400        
Promethazine (PMT) Fe(III)-SCN-- PMT 160 - 550        
Chlorpromazine (CPZ) Co(II)-SCN--CPZ ether 620 - 100 - 600 52
Chloracizine (CRZ) Co(II)-SCN--CRZ 100 - 900        
Chlorpromazine (CPZ) Ge(IV)-PCV-CPZ cyclohexa-none 580 6.8 ·103 Jul-70 53
Chlorpromazine (CPZ) Sn(IV)-PCV-CPZ butanol 580 - 20-Feb 31
Desipramine (DE) Ti(IV)- SCN- - DE chloroform 355 5.85 ·10-4 5 – 200 54
Thioridazine (TR) Ti(IV) – SCN-- TR chloroform - 417 - 20 - 160  
Perazine (PZ) Ti(IV) – SCN-- PZ butanol (4:1) 360 8.96·103 20 – 170 55
Amitriptyline (AM) Ti(IV) – SCN-- AM 3 – 60        
Promazine (PM) Nb(V)-SCN--PM trichloro-ethylene 400 - 20 – 200 56
Imipramine (IM) Nb(V)- SCN- - IM butanol-chloroform (1:9) 350 6.67∙10-4 0.8 - 8 43
Doxepin (DX) Ti(IV)- SCN- - DX butanol-chloroform (2:3) 400 7.12· 103 5 – 50 44
Chlorprothixene (CX) Nb(V)- SCN- - CX butanol 362 8·103 Sep-50 46

Table2: Detrmination of psychotropic drugs in ternary systems.

Materials and Methods

Recently Misiuk [44] studied the ion association compounds of doxepin (DX) with thiocyanate complexes of titanium (IV) and iron (III). The produced compounds were insoluble in water, but well soluble in some organic solvents. They were quantitatively extracted with a mixture of butanolchloroform (2:3) and (1:4) using titanium (IV) and iron (III) thiocyanates, respectively. The mentioned properties were applied for the elaboration of new spectrophotometric methods for the determination of doxepin in DX-Ti-SCN- and DX-Fe-SCN- systems, respectively. The proposed methods have been successfully applied for the determination of the main active ingredient in different dosage forms. The method can also be used for the determination of doxepin in the presence of its degradation product, dibenzo [b,e]oxepin-11-(6H)-one. The dibenzo [b,e] oxepin-11-(6H)–one was examined by TLC, UV and IR techniques. The precision, accuracy and reproducibility of the methods were good and RSD values were low.

It has been found that imipramine and chlorprothixene react with thiocyanate complexes of niobium (V) forming yellow sparingly soluble in water compound in a molar ratio of 1:2 of Nb (V):each drug [43,46]. These compounds can be quantitatively extracted with chloroform-butanol (1:9) or butanol alone. The spectrophotometric methods have been developed for the determination of imipramine and chlorprothixene in the ranges of 0.8-8 ppm and 9-50 ppm, respectively.

Desipramine forms a compound of the ion pair type with thiocyanate complexes of titanium (IV) [54] in acid medium, which can be quantitatively extracted with chloroform. The properties have been used for the spectrophotometric determination of desipramine in the range of 5 - 200 ppm.

Chlorpromazine (CPZ) forms a yellow sparingly soluble in water compound of molar ratio of 1:1 (λmax = 445 nm) with pyrocatechol violet (PCV) in an acid medium [31]. The drug also reacts with tin(IV) ions in the presence of pyrocatechol violet, in aqueous phase at the molar ratio Sn(IV):PCV:CPZ = 1:2:2, and in the organic phase at the ratio 1:2:4 (λmax = 580 nm). These compounds can be quantitatively extracted from aqueous solutions with chloroform-butanol (5:1) or butanol alone. Taking advantage of these properties, the spectrophotometric methods for the determination of chlorpromazine have been developed. The methods proved suitable for assaying chlorpromazine in the range of its concentrations from 3.5 ppm to 35 ppm and from 2 ppm to 20 ppm, respectively. The reaction in the systems chlorpromazine-chrome azurol S [27] and germanium (IV)-pyrocatechol violet-chlorpromazine [53] were applied for CPZ determination in the concentration range 2-20 ppm and 7-70 ppm, respectively.

Fluoxetine and fluvoxamine were determined spectrophotometrically using chrome azurol S and eriochrome cyanine R [12,13]. These dyes react in aqueous media with studied psychotropic drugs forming colored, sparingly soluble in water complexes. These complexes can be quantitatively extracted with chloroform or chloroform-buthanol (3:1). Gindy et al. [11] described the methods for the determination of trazodone in pharmaceutical preparations. The spectrophotometric and spectrofluorimetric methods were based on the formation of yellow ion pair complex between the basic nitrogen of the drug and bromophenol blue. The formed complex was extracted with chloroform and the absorbance was measured at 414 nm. The suggested mechanism of trazodone – bromophenol blue ion pair complex is presented in Scheme 3.


Scheme 3: Mechanism of ion pair complex trazodone-bromophenol blue system

Electrochemical methods

Psychotropic active substances are easily oxidized (e.g., dibenzoazepines, thioxanthenes, phenothiazines) or reduced (e.g., trazodone, sertraline, paroxetine), electrochemically. The first step in the electrochemical oxidation of phenothiazine and azaphenothiazine derivatives occurs at the sulphur atom, while the second wave is attributed to the transformation of the radical cation into a dication [5]. The mechanism of the oxidation of thioxanthenes is not fully understood, but the potentials and peaks shapes of the thioxanthene derivatives are similar to those of the phenothiazine derivatives, the first oxidation wave involving two-electron oxidation to the sulphoxide [1].

The dibenzoazepines are the most easily oxidized, the first electron is removed from the monomer nitrogen and the radical can then exist in a number of resonance forms. The monocation rapidly dimerises or reacts with an unoxidised molecule. The dimerisation is accompanied by the loss of two protons per dimer. The dimer is more easily oxidized than the monomer [57].

Electrochemical oxidation of some active substances is exploited for using these substances in polarographic and voltammetric analysis. Several electrochemical techniques have been applied for the determination of psychotropic substances in drugs preparations and differential biological samples [58-60]. Oelschlager [59] reviewed the polarographic methods reported for psychotropic drugs including phenothiazine and azaphenothiazine derivatives. Temsamani et al. [61] have analyzed chlorpromazine in plasma by using cyclic voltammetry and modified gold electrode. Chlorpromazine has been determined in urine samples of patients by adsorptive stripping voltammetry in the presence of Triton X-100 [62]. Fluphenazine and trifluoperazine were determined by differential pulse voltammetry after pre-concentration at a wax-impregnated graphite electrode. For plasma, the electrode was covered with a membrane to prevent fouling by proteins [63]. Alternatively, promazine, chlorpromazine and promethazine spiked in urine samples were oxidized by nitrous acid into the corresponding sulphoxides, which were polarographically active. They produce well-defined diffusion-controlled cathodic wave [58].

The dibenzoazepine derivatives, e.g. imipramine, clomipramine and trimipramine were determined in drugs preparations and plasma samples with adsorptive stripping voltammetry [64,65]. Imipramine and desipramine were analysed by cyclic voltammetry at glassy carbon and boron-doped diamond electrode [66]. Wang et al. [67] determined imipramine and trimipramine in urine sample by using cyclic voltammetry and differential pulse voltammetry. Among thioxanthene derivatives, zuclopenthixol was determined quantitatively by measuring the height of voltammetric peaks. The oxidative voltammetric behaviour of zuclopenthixol at a glassy carbon electrode has been studied using cyclic, linear sweep and differential pulse voltammetry [68]. Tuzhi et al. [69] reported an adsorptive pre-concentration method for the voltammetric measurement of trace levels of chlorprothixene. Alternatively, chlorprothixene and thiothixene were determined polarographically through the formation of their bromo-derivatives, which manifest well defined cathodic waves in select supporting electrolytes [70].

Trazodone, which is a triazolopyridine derivative, unlike the tricyclic antidepressants was studied using direct current, differential pulse and alternating current polarography [71]. It was concluded that, only the carbonyl group was involved in the reduction process according to the mechanism given in fig. 2. The proposed method was successfully applied to the determination of the trazodone in pure form and in formulations and the biological fluids (human urine and plasma).


Fig. 2: Mechanism of electroreduction of trazodone

A review of the electrochemical methods for the determination of some psychotropic drugs (e.g. phenothiazines, azaphenothiazines, dibenzoazepines, thioxanthenes) [68,72-89] is presented in Table 3 and the electrochemical methods for the determination of new atypical psychotropic drugs (e.g. olanzapine, sertraline, trazodone) [90-92] are given in Table 4.

Psychotropic drug Medium Method Working
Range of
Chlorpromazine, Britton's buffer, pH=2-7 DPP Hg 6·10-6 - 1·10-4 3·10-7 Drug 58
Promazine,       5·10-6 - 8·10-5 3·10-7 preparations  
Promethazine       8·10-6 - 1·10-4 4·10-7 Urine  
Chlorpromazine 0.2 M H2S04, LSV Ru 2·10-4 - 8·10-4 - Drugs preparations 72
Thioridazine 0.2 M H2S04, CV Pt, 5·10-5 - 1·10-3 - Drugs preparations 73
      Ru, 6·10-4 - 1·10-2      
      GC 1·10-4 - 1·10-3      
Fluphenazine 0.5 MI-1,504, CV Pt, 4·10-4 - 1·10-2 - Drugs preparations 74
  Phosphate buffer, pH=6.2     2·10-4 - 4·10-3      
  0.5 M H250,   GC 2·10-5 - 8·10-4      
Promazine, 0.1MHCl LSV CPE, 2.5·10-5- 5·10-3 - Drugs preparations 75
Promethazine,     SCPE 2.5·10-5- 5·10-3      
Levomepromazine     GC 6.2·10-5-1.2·10-3      
Chlorpromazine, Thioridazine 0.1 M IIaCl0,
in acetonitrile
DPV Pt 7·10-7 -1.4·10-5 4·10-7 Drugs preparations 76
Chlorpromazine, Britton's buffer, pH=7.0
(in the presence
of Triton X-100)
AdSV Hg 2·10-8 -5·10-6 4.2·10-9 Drugs preparations
Ethopropazine 0.05 M Phthalate
buffer, pH=3.5
CV Au 4·10-7 - 4·10-6     77
  (in the presence of SDS)       -    
Promethiazine, Phosphate buffer, pH=7 DPV WIGE 5·10-7 – 1·10-4 5·10-8 Urine, plasma 63
Diethazine,         -    
Chlorpromazine Phosphate buffer, pH=7 DPV WIGE 4.8·10-8 – 2.4·10-4 5·10-9 Urine 78
Chlorpromazine, 0.1 M Phosphate AdSV CPE 8.3·10-8 – 2·10-6 1·10-9 Urine, 79,
Perphenazine, buffer, pH=7.4 DPV       blood samples 80
Chlorpromazine 0.1 M Phosphate AdSV CPE 1.5·10-6 – 9·10-6 1·10-7 Urine 81
  buffer, pH=7.4 DPV          
Chlorpromazine, Britton's buffer, pH=9 AdSV GC 1.5·10-7 – 3.4·10-6 1.3·10-7 Blood 82
Promethiazine   DPV   3·10-7 – 3·10-6 1.2·10-7 samples  
Phenothiazine, Acetate buffer, CV MCPE 2·10-8 – 3·10-7 1.2·10-8 Drugs' 83
Chlorpromazine, promethiazine pH=5.0       7·10-9
Thioridazine, Acetate buffer, DPV MCPE 1·10-7 - 1·10-6 4.5·10-8 Drugs' 84
Prochlorperazine, pH=5       1.2·10-8 preparations  
Chlorpromazine, Phosphate DPV MCPE 1.96·10-7 1·10-7 Model 64
Thioridazine, buffer, pH=7.4     2.75·10-6 7·10-8 serum  
Prochlorperazine,         4·10-8    
Levomepromazine         8·10-8    
Thioridazine Phosphate
buffer, pH=6.6
MCPE 1·10-8 - 1·10-7 7·10-9 Drugs'
Fluphenazine 0.05 M HCOOH-
HCOOHa buffer, pH=3.5
CV MAu 5·10-8 - 1.5·10-5 1·10-8 Drugs'
Perphenazine 0.05 M borate CV MAu 5·10-7 - 5·10-6   Drugs' 86
  buffer, pH=10.0     6·10-6 - 5·10-5 - preparations  
Chlorpromazine 0.05 M Phosphate
buffer, pH=9
CV MAu 2·10-7 - 3·10-5 - Biological
Promazine, Promethiazine, Acetate buffer, pH=4.7 CV,
2·10-7 - 3·10-5 down to 1·10-8 Drugs'
Prothipendyl Britton's buffer,
DPP Hg   - Blood, plasma,
Imipramine 0.1 M H2504,
Phosphate buffer,
CV MCPE 2·10-7 - 3·10-5 - Drugs'
Imipramine, Trimipramine Phosphate buffer,
MCPE 1.10'-1.10° 2·10-8 Drugs'
Imipramine, Phosphate buffer, DPV MCPE 6·10-5 - 8·10-4 1·10-7 Plasma 64
Trimipramine, pH=7.4       1.1·10-7    
Clomipramine         0.5·10-7    
Imipramine Phosphate buffer,
LSV MCPE 1·10-7 - 8·10-6   Drugs'
Imipramine, Acetate buffer, DPV 1·10-7 - 8·10-6 8.5 ·10-8 Drugs' 84
Clomipramine, pH=5       9.2 ·10-8 preparations  
Trimipramine         9.0 ·10-8    
  pH=9         preparations,
Imipramine, Acetate buffer, DPV MCPE 1·10-7 - 1·10-6 8.5 ·10-8 Drugs' 84
Clomipramine, pH=5       9.2 ·10-8 preparations  
Trimipramine         9.0 ·10-8    
Imipramine, Phosphate buffer, CV, CPE, 2·10-7 - 6·10-7 1.5·10-8 Urine 67
Desipramine, pH=9 DPV GC 2·10-7 - 6·10-7 1.7·10-8    
Trimipramine       2·10-7 - 1.6·10-6 1.4·10-8    
Clomipramine Britton's buffer,
phosphate buffer
SWP Hg - - Drugs' preparations 89
Imipramine, Clomipramine, Phosphate buffer,
- - Plasma 66
Imipramine, Clomipramine, 0.1 E1250,, ISV,
- -   57
Zuclopenthixot 0.1 M H,S0,
Britton's buffer,
pH=2.0 - 11.5,
phosphate buffer,
pH=5.2 - 8.3
GC 8·10-7 - 2·10-4 2.2·10-7 Drugs' preparations 68
Chlorprothixene Britton's buffer,
CV, DPV GC 0.1 - 1 μg/ml time of
condition =30s
0.01 - 1 μg/ml
time of
condition = 120 s
- Urine 69
Chlorprothixene, Thiothixene 0.1 M HCl,
Britton's buffer,
dc-P Hg 2.7·10-5 - 1·10-4 - Drugs' preparations 70

Table 3: Voltammetric Analysis Of Psychotropic Drugs

Psychotropic drug Medium Method Working electrode Range of determination [mol/l] LOD [mol/l] Practical application Ref.
Olanzapine Phosphate buffer, pH=2.5 LSV GC 1.97·10-5-1.59·10-4 9.54·10-6 Drugs preparations 90
Fluoxetine Ringer buffer, pH=12   AdSV Hg     - 91
CV,   - -    
DPV   - -    
SWV   5.2·10-5 -5.2·10-5 3.9·10-8    
Paroxetine Borate buffer,pH=8.8 AdSV, Hg 3·10-6  - 1.7·10-5 4.8·10-7 Drugs preparations 17
Trazodone Britton’s buffer,pH=10 ac-P, Hg - - Urine, plasma 71
dc-P, DPV   9.8·10-6  -7.8·10-5 7.69·10-7    
      1.9·10-6  -5.8·10-5 2.54·10-7    
Sertraline Borate buffer,pH=8.2 FIA Hg 2·10-7  -1.2·10-6 1.5·10-7 Drugs preparations 18
Sertraline Borate buffer,pH=8.2 AdSV Hg 2.33·10-7 -  3.15·10-6 1.98·10-7 Drugs preparations 92

Table 4: Voltammetric Analysis Of Atypical Psychotropic Drugs


Psychotropic drugs, e.g. dibenzoazepines, dibenzocycloheptadienes, thioxanthenes, and phenothiazines, and new generation drugs, e.g. fluoxetine, fluvoxamine, and trazodone form cations which react with some organic substances (picric acid, flavianic acid, alizarin S, brilliant blue, and triphenylmethane dyes) and thiocyanate or halide anionic complexes (e.g. Co(II), Pd(II), Fe(III), Cr(III), Au(III), Ti(IV), Pt(IV), Mo(V), W(V), U(VI) forming ion-association compounds. The compounds get precipitated from aqueous solutions and can be quantitatively extracted into organic solvents (e.g. chloroform, dichloromethane and butanol). The extracts are intensely colored and stable for 1-3 days. These properties have been applied for the determination of above - mentioned metal ions and active compounds in pharmaceutical preparations.

As mentioned previously, the official compendia [93] recommends determination of psychotropic active substances in bulk or in pharmaceutical forms by measurement of the absorbance at selected wavelengths, or titration in a non–aqueous medium with potentiometric or visual indication at the endpoint. The proposed pharmacopoeial procedures require intensive isolation and purification steps in the case of the assay of the studied psychotropic substances in their pharmaceutical dosage forms. The main disadvantage of direct UV spectrophotometry is the sensitivity to excipients usually presented in pharmaceutical formulations.

In the presented review, methods based on the complexation reactions are discussed as alternative methods. The absorbance of colored ion association complexes of psychotropic drugs are less liable to spectral interferences from other ingredients of pharmaceuticals. The reviewed methods offer advantages of their simplicity, rapidity and common access to instrumentation. The analytical methods for the determination of psychotropic drugs are characterized with good precision, sensitivity and reproducibility.

Electrochemical methods have also been used for the study and determination of some psychotropic drugs. Among the methods, mainly used are voltammetry - cyclic voltammetry and differential pulse voltammetry, after pre-concentration of studied substances at several kinds of bare surfaces of electrodes, e.g. glassy carbon electrode, carbon paste electrodes or using different modified electrodes. Procedures have been described in literature for the determination of dibenzoazepines, dibenzocycloheptadienes, thioxanthenes, phenothiazines and new generation psychotropic drugs such as olanzapine, fluoxetine, paroxetine, trazodone, sertraline. Those are projected to be simple, fast and sensitive, which can be applied successfully to determine active substances, their metabolites in pharmaceutical formulations and biological fluids.