Chemiluminescence of copper nanoclusters and its application for trihexyphenidyl hydrochloride detection.

Chemiluminescence (CL) of copper nanoclusters (CuNCs) induced by cerium (IV) (Ce(IV)) or potassium permanganate (KMnO4 ) in acidic medium was observed. The potential application of CuNCs CL in analytical chemistry was also demonstrated using trihexyphenidyl hydrochloride (THP) as an example based on its enhancing CL intensity for the CuNCs-Ce(IV)/KMnO4 systems. The excited state of the CuNCs acted as a luminophore in the CuNCs-Ce(IV) system, while CuNCs played the role of reductant in the CuNCs-KMnO4 system. The increased CL intensity for Ce(IV)-CuNCs system was proportional to the THP concentrations in the range of 0.1 to 10.0 µM. The detection limit was 49.0 nM and the relative standard deviation was 2.2% for 2.0 µM THP (n = 11). The proposed method was applied to detect THP in pharmaceutical formulations and human plasma samples.

Fatal intoxication because of trihexyphenidyl.

Trihexyphenidyl (THP) is an anticholinergic agent with forensic toxicological interest. We present a case of a 59-year-old woman with a history of paranoid disorder, who was found dead in the house where she lived alone. The autopsy findings revealed no marked pathological changes. Toxicological analysis based on gas chromatography-mass spectrometry (GC-MS) analysis revealed THP and its major metabolite (hydroxy-THP) in blood and urine, with THP concentrations of 0.053 and 0.560 mg/L, respectively. The blood and urine ethanol concentrations were low 0.096 and 0.100 g/L, respectively. Based on these results, we determined the cause of death to be THP poisoning. It is suggested that rare case of death associated with THP overdosage should be taken in conjunction with central nervous system depressants (benzodiazepines, ethanol) and/or with other pathological disorders. Thus, our case could not be supportive for this allegation.

Flow injection determination of benzhexol based on its sensitizing effect on the chemiluminescent reaction of Ce(IV)-sulfite.

In this paper, a novel chemiluminescent (CL) method for the determination of benzhexol has been developed by combining the flow injection technique and its sensitizing effect on the weak CL reaction between sulfite and acidic cerium(IV). A mechanism for the CL reaction has been proposed on the basis of CL spectra. Under the optimized conditions, the proposed method allows the measurement of benzhexol hydrochloride over the range 0.1-10 microg/mL with a correlation coefficient of 0.9992 (n = 8), a detection limit of 0.02 microg/mL (3sigma), and a relative standard deviation for 2.0 microg/mL benzhexol (n = 11) of 1.65%. The utility of this method was demonstrated by determining benzhexol hydrochloride in tablets.

Drug-human serum albumin binding studied by capillary electrophoresis with electrochemiluminescence detection.

A new technique for investigating drug-protein binding was developed employing capillary electrophoresis (CE) coupled with tris(2,2'-bipyridyl) ruthenium(II) [Ru(bpy)(3) (2+)] electrochemiluminescence (ECL) (CE-ECL) detection after equilibrium dialysis. Three basic drugs, namely pridinol, procyclidine and its analogue trihexyphenidyl, were successfully separated by capillary zone electrophoresis with end-column Ru(bpy)(3) (2+) ECL detection. The relative drug binding to human serum albumin (HSA) for each single drug as well as for the three drugs binding simultaneously was calculated. It was found that the three antiparkinsonian drugs compete for the same binding site on HSA. This work demonstrated that Ru(bpy)(3) (2+) CE-ECL can be a suitable technique for studying drug-protein binding.

Development of a screening method for the most commonly abused anticholinergic drugs in Jordan; trihexyphenidyl, procyclidine and biperiden.

A sensitive and rapid method for the simultaneous determination of three commonly abused anticholinergic drugs in Jordan; trihexyphenidyl, procyclidine, and biperiden in plasma and urine has been developed using solid phase extraction and GC-MS. Linearity was established from therapeutic to fatal concentrations of the three drugs; 5-300 ng/ml in plasma, with correlation coefficient r(2) > or = 0.9978 and 10-800 ng/ml in urine r(2) > or = 0.9993. Recoveries were in the range of 86-92% and intra-day and inter-day relative standard deviations (n = 6) were in the range of 6.6-10.3% for the three drugs at three different concentrations in plasma and urine. The base peak m/z 98 for trihexyphenidyl, m/z 84 for procyclidine, and m/z 98 and 218 for biperiden, and m/z 339 for papaverine (internal standard) were monitored at selective ion monitoring; their retention times were 8.10, 8.67 and 8.92 min, respectively, and 14.79 min for the internal standard with analysis time of 16.75 min. The limit of detection of 0.5 ng/ml was attained for trihexyphenidyl and procyclidine, while for biperiden 2.0 and 1.0 ng/ml in spiked plasma and urine, respectively. This method has been applied to forensic and authentic samples taken from abuser and patients using these drugs. The method will offer the clinicians and the legal authority the right diagnosis regarding the anticholinergic involved in any case of abuse with less than 1 h per sample (plasma or urine) from the time of receiving.

Stereoselective determination of trihexyphenidyl in human serum by LC-ESI-MS.

The antiparkinsonian drug trihexyphenidyl (THP) is currently manufactured and administered as a racemate. However, stereochemistry can play significant role in the drug's pharmacokinetics, biotransformation, metabolism, interaction with cellular and tissue components and overall effect on human body. It is necessary to consider such a drug as a mixture of two compounds (drug enantiomers), with their own effect on the human body. The present paper describes a simple and sensitive LC-MS method for the stereoselective determination of THP in human serum. In this study, the sample was prepared by a solid-phase extraction (SPE) procedure. The enantiomer separation was done using native beta-cyclodextrin stationary phase LC column. The combination of ESI-MS detection and SPE showed excellent sensitivity and selectivity of the method. The limits of detection of <0.1 ng/ml can be easily achieved, which is 7,000 times lower than the detection limits achievable by a UV detection method. The method has at least a 3-order of magnitude linear dynamic range for both enantiomers (concentrations up to 1,323 ng/ml were tested). This is 24 times wider than the therapeutic range of THP (peak THP plasma concentration of 55 ng/ml was previously reported). The recoveries of THP enantiomers from the human serum were > 95%.

A widely applicable electrode sensitive to basic drugs based on poly(vinyl chloride) membrane plasticized with tricresyl phosphate.

A plastic membrane ion-selective electrode applicable to many basic drugs has been developed. The electrode developed was constructed with tricresyl phosphate and a poly(vinyl chloride) matrix on a polytetrafluoroethylene film. The electrode showed a near-Nernstian response to chlorpromazine, trihexyphenidyl, imipramine, dibucaine, papaverine, propranolol, tetracaine, trazodone, quinidine and cinnarizine. The determination of 50 to 3000 micrograms/ml of trazodone hydrochloride in a pH 4.0 acetate buffer solution showed an average recovery of 99.4% (mean standard deviation 0.7%) by direct potentiometry. Inorganic cations and pharmaceutical excipients did not interfere with the determination. Trazodone hydrochloride and trihexyphenidyl hydrochloride in tablets were determined, and the results compared favorably with those obtained by conventional methods.

Capillary gas chromatography of trihexyphenidyl, procyclidine and cycrimine in biological fluids.

A sensitive (50-100 pg/ml) method is described for the analysis of the anticholinergic drugs cycrimine, procyclidine and trihexyphenidyl by capillary gas chromatography with flame thermionic detection. Since these anticholinergic drugs are frequently administered in combination with antipsychotic medication for the treatment of mental illness, the potential interference by antipsychotic drugs in this assay was examined. No interference was observed from a series of antipsychotic drugs in the quantitation of cycrimine, procyclidine or trihexyphenidyl. The use of this technique to study trihexyphenidyl pharmacokinetics in man is described.

Identification and quantification of trihexyphenidyl and its hydroxylated metabolite by gas chromatography with nitrogen-phosphorus detection.

A sensitive and specific assay for the simultaneous quantification of trihexyphenidyl and its hydroxylated metabolite in plasma and urine is described. The method is based on the extraction of the drugs with an organic solvent and separation on a 3% OV-17 Chromosorb Q column in a gas chromatograph equipped with a nitrogen-phosphorus detector. The procedure employs SKF 525 A as the internal standard and requires no derivatization. The detection limit was found to be 2 ng/mL for trihexyphenidyl and 1 ng/mL for its metabolite. The precision of the assay procedure for both compounds is about 4 to 7%.

Impurities in drugs III: Trihexyphenidyl.

Two lots of trihexyphenidyl hydrochloride raw material, one lot of elixir, and 10 lots of tablets were examined for impurities by TLC. Impurities found were 1-phenyl-2-propenone, 3-piperidinopropiophenone, and 3-aminopropiophenone. Not all impurities were present in all lots, and none exceeded 1.9% of the label drug claim. Impurities were identified by mass spectrometry and by comparison of TLC Rf values and GLC retention times to those of synthesized specimens of the impurities.

GLC determination of trihexyphenidyl hydrochloride dosage forms.

A rapid, sensitive, and specific GLC method for the quantitation of trihexyphenidyl hydrochloride in various pharmaceutical dosage forms is described. The procedure involves chloroform extraction of the active ingredient from a weakly acidic solution, followed by GLC determination using a 3% methyl silicone column. The specificity of the system in relation to several compendial drug analogs also is reported.

Benzhexol and side effects with long-acting fluphenazine therapy.

Sixteen patients who had for some months been on fluphenazine enanthate injections (1-3 ml) every two or three weeks, with daily oral benzhexol (6-40 mg), were divided into two groups comparable in age, diagnostic category, and drug dose.Placebo was substituted under blind controlled conditions for benzhexol in one group, and both groups were regularly assessed by Simpson rating scale for extra-pyramidal signs, and by a 30-question symptom check list. Both assessments were found reliable.Four out of eight patients had severe reactions when off benzhexol, but symptoms such as tremor and daytime sleepiness were unaltered in all patients. The other four did not suffer adversely from withdrawal of benzhexol.Acute withdrawal is therefore unjustified, but occasional revision of dosage of anti-Parkinsonian drugs is advisable. There is no evidence that tolerance develops to any effect of a phenothiazine, but long-continued benzhexol might induce a denervation supersensitivity. It is also possible that Parkinsonian signs are dependent on affective state.