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The most important steps in the validation of high-performance liquid chromatographic (HPLC) methods are discussed. The establishment of system suitability data and the assessment of peak purity are demonstrated on the example of bisquaternary amino steroids. For the recognition of incomplete resolution of adjacent peak pairs, the absorbance-ratio method in which the ratio of absorbances at two preselected wavelengths are plotted as a function of time in combination with the separation of sample components subjected to various chemical and physico-chemical treatments (stress conditions) is applied. The separation power and performance of the HPLC systems are characterized by the system resolution (SR) and system selectivity (SS). The special demands of stability-indicating methods are summarized.

In order to compare tracheal intubation conditions, 34 adult patients about to undergo elective surgery received at random atracurium 0.5 mg X kg-1, pipecuronium 0.1 mg X kg-1 or vecuronium 0.1 mg X kg-1, intravenously. Intubation was attempted when only the first of the train-of-four finger contractions, arising from ulnar nerve stimulation, remained. The three relaxants provided effective conditions for intubation. The time required to suppress all but the first train-of-four response was shortest in the group given atracurium (P less than 0.05). Compound muscle action potentials (emg) were continuously filmed from just before induction of anesthesia until the trachea was intubated. The degree of neuromuscular blockade was similar in the three study groups.

Acute toxicity studies with 2 beta,16 beta-bis(4'-dimethyl-1'-piperazino)-3 alpha,17 beta-diacetoxy-5 alpha-androstane dibromide (pipecurium bromide, RGH-1106, Arduan), a new neuromuscular blocking agent, revealed an order of sensitivity as follows: rabbits greater than mice greater than rats. Subchronic toxicity was tested on conscious dogs by 20 daily doses of 150 microgram/kg i.v. corresponding to 4-fold the planned clinical dose followed by daily intubation and artificial ventilation until recovery of spontaneous respiration. Dosage was limited by prolonged paralysis time requiring artificial ventilation. Apart from daily stress of paralysis preceding intubation no irreversible toxic changes were detected by laboratory and morphological tests. ECG changes were restricted to paralysis time, they were characterized by transitory arrhythmia and variation of the ST-segment. In additional studies on conscious and unconscious dogs no lethal ECG changes could be induced with cumulative dose totalling 10 mg/kg i.v. Short-term in vivo and in vitro mutagen tests did not reveal either mutagenic and clastogenic effects or increase of chromosomal aberrations. Intravenous local tolerance in rats was satisfactory.